EP0716703A1

EP0716703A1 - Glycophorin binding protein (gbp130) fusion compositions

Info

Publication number: EP0716703A1
Application number: EP94924961A
Authority: EP
Inventors: Kenneth Francis Prendergast
Original assignee: Individual
Current assignee: Individual
Priority date: 1993-09-03
Filing date: 1994-09-01
Publication date: 1996-06-19
Also published as: WO1995006737A1

Abstract

Hybrid or fusion peptides formed by the fusion of two or more peptide components, where one component is derived from or is all or part of a malaria parasite red blood cell binding peptide, and the other peptide being a receptor for or capable of binding to a cytokine or other mediator of inflammation or immunity. The fusion peptides find a use in the treatment of septic shock, AIDS, and inflammatory conditions. The fusion peptides also serve as potential testing agents for use in inflammatory conditions and septic shock.

Description

GLYC0PH0RIN BINDING PROTEIN (GBP130) FUSION COMPOSITIONS

The Field of the Invention;

The field of the present disclosure relates to hybrid therapeutic peptides having the property of lowering the levels of free Tumour Necrosis Factor α and β in the circulation and other harmful cytokines, thus, modifying the pathological damage caused by Tumour Necrosis Factor, and finding a use in the treatment of diseases especially but not only septic shock; bacterial meningitis' cerebral malaria, HIV, SVHD graft versus host disease and pulmonary fibrosis. The present disclosure is an extension the teachings of PCT 93/00505 Anti viral fusion peptides whose teachings are incorporated herein fully by reference, which PCT was published as WO93/18160 after the filing date of the priority document GB93 19350.7.

Background Art

Tumour necrosis factor herein after referred to as TNF is an extremely potent peptide produced in 2 forms, TNFα produced by activated macrophages and TNFβ produced by activated lymphocytes. Both α and β varieties have similar spectra of biological effects, however, TNFα is byfar the more powerful of the two. The effects of TNF are mediated by binding to specific receptors found on the surface of most cells. As a naturally produced agent TNF has important biological roles to fulfil. Physiologically TNF is classified as a cytokine. It's effects on the immune system are to increase neutrophylia and activate macrophages, and increase the production of T cells in the thymus.

The term TNF tumour necroses factor was attributed to this peptide by Old arising from the observation that TNF can reduce necrosis and regression of experimental sarcomas in mice.

It is likely that TNF serves to eliminate small tumours from the host at an early stage in their development. Clinically cloned TNF has been used to treat human tumours especially melanoma. It has also been shown that TNF is more effective against tumours when used in combination with other cytokines IL2 or γlFN gamma interferon. Talmadge J et al Am. J of Pathology, Vol 128, No 3, Sept 1987; 410-425.

After administration of TNF microembili and haemorrhagic necrosis are produced in the substrate of the tumour leading to it's regression. However, this endogenously produced potent peptide is not always helpful to the host and may be harmful.

Following intestinal surgery a number of patients succumb to endotoxic shock, a syndrome of refractory shock and small vessel changes. Shown experimentally to follow the administration of LPS, bacterial lipopolysaccharide constituent of the cell wall of gram negative bacteriae. Morrison D C et al, Am. J. Pathology, 93: 527-617: 1978. The syndrome of endotoxic shock shares many features in common with the effects seen after administration of TNF. It is now believed that LPS acts indirectly and causes shock via the production of TNF. Indeed, the administration of LPS to animals has been shown to cause a rise in TNF levels 200 minutes later. Mathison J et al, J. Clin. Invest., Vol 81: June 1988: 1925-1937.

The process of intestinal surgery or abdominal trauma leads to the release of gram negative organisms into the circulation. Gram negative cell wall lipopoiysaccaride is a very potent agent capable of inducing a shock syndrome in low doses. Humans are exquisitely sensitive to LPS. LPS has 3 components: Lipid A - R core - polysaccharide. The polysaccharide part varies with the species and strain of the infecting organism. The active moiety of endotoxin is now believed to be Lipid A.

The clinical picture of 'septic shock' or 'endotoxic shock' is one of hopelessness. Some 100,000 North Americans die annually from this pathological process which occurs with an incidence of 200,000 to 400,000. Despite active management it is difficult to rescue a situation in which the clinical picture is one of descent from shock to multiple organ failure to death. Notwithstanding fluid support and pressor therapy with dopamine, cardiac output falls from direct cardiac suppression and low venous return. All fluid support provided redistributes into dilated capillary spaces where it sludges. The provision of such intensive treatment in a Critical Care Unit is expensive. A need exists for agents capable of preventing endotoxic shock, for treating septic shock, and also for diagnosing this entity so that treatment may be better planned. One is directed to the reviews of C J Schmeichel et al, Biotechnology, Vol 10, March 1992, 264-267 and to J Pavrillo et al, Annals of Internal Medicine, Vol 113, No 3, (1990) p227-242.

The rise of TNF levels seen in mice after injection of bacterial lipopolysaccharide LPS have also been seen in humans.

Similar experiments in healthy humans demonstrated a brief pulse of TNF production 90- 180 minutes afterthe administration of endotoxin. Mitchie H R et al, N. Engl. J. Med., 1988: 318: 1481-6.

The observations of Mitchie are important in explaining the inconsistency of TNF assays in septic shock patients. Pulsed production of this cytokine ties in with the notion that TNF initiates the vascular responses in septic shock and explains why it is not always detected in serological assays. However, elevated TNF levels have been convincingly associated with mortality in the critically ill. J Bebets et al, Crit. Care Med., 1989, 17: 489. More convincingly Remick et al demonstrated and quantified an increase in TNF mRNA in mice after LPS administration. Remick D G et al, Am. J. Pathology, 1990; 136: 49-60.

Patients with septic shock exhibiting the Adult Respiratory Distress Syndrome, ARDS, havo demonstrated higher plasma TNF levels - which in turn are associated with increased mortality. J D Marks et al, Am. Rev. Respir. Dis., 1990; 141: 94-97. Evidence mounts for a role played by TNF in other pathological entities, such as rheumatoid arthritis; the rejection of transplants and GVHD graft venous host disease, Kunkel S L et al, 1991, Biotherapy3, 135-141. In the case ofmalaria higher TNF levels are associated with cerebral malaria, see Grau G E et al (1987), Science 237, 1210-1212, and Grau G E, Eur. Cytokine Network 1, 203-210.

Further research suggests that TNF may produce a significant part of the pathological spectrum of AIDS.

The severe and rapid wasting of AIDS patients towards the end of their illness but not seen during years of asymptomatic viral carriage, led workers to suspect that some agent other than the virus itself may be responsible for this process. TNF already suspected as the cause of weight loss and cachexia in cancer and previously named "cachectin" was a prime suspect. Lahdevirta et al were able to demonstrate substantially raised serum TNF levels in AIDS patients several fold higher than in asymptomatic subjects. Lahdeverta J et al, Am. J. of Med., Vol 85, (1988) 289-291. Lahdeverta also pointed out that the raised TNF levels may be the result of persistent infection load seen in these patients harbouring at any one time chronic fungal, viral, parasitic and bacterial infestations. Indeed, other workers suggested that chronic sepsis raises TNF which in turn raises HIV viral titres thus creating a vicious circle. Osborn L et al proved this point, see Proc. Natl. Acad. Sci. USA, Vol 86, pp 2336-2340 (1989), by demonstrating that TNFα and also IL1 interleukin 1 increase HIV production in infected cells and that this effect is produced via NF-KB Nuclear Factor Kappa B which intracellular messenger stimulates H IV production and also ιeappa immuno globulin light chain productions.

F Staal et al were able to demonstrate that intracellular thiols, more particularly GSH (gamma-glulamylcysteinglycine the most abundant), suppress NF-KB production and mitigate the effects of TNFα levels are elevated. Staal F, Proc. Nalt. Acad. Sci. Usa, Vol 87, pp 9943-9947, Dec 1990.

By blocking TNFα in vitro using anti-TNFα antibodies, the HIV production induced by TNFα can be reduced. Moreover, observers now suspect an amplification mechanism whereby TNFα leads to further production of it's own receptor and also production of IL6 (interleukin 6) which interleukin may prolong the process and continue to stimulate viral production when TNF is no longer available. Poli G et al, Proc. Nalt. Acad. Sci. USA, Vol 87, pp 782- 785, Jan 90.

The agent methylxanthine pentoxyfylline is known to suppress TNFα levels in vivo. In vitro this agent has been demonstrated to reduce the replication of HIV in cultured cells. It's use in AIDS treatment in conjunction with the agent AZT was suggested by F Fazely et al, Blood, Vol 77, No 8, April 15 1991: pp 1653-1656.

The benefit of TNFα reduction in AIDS patients cannot be over stressed. TNFα is known to suppress haematopoiesis, of itself, and via IL2 interleukin 2, levels of which are raised by TNFα. Moreover TNFβ is a powerful suppressor of red cell production and this too is elevated in AIDS, as reviewed by J Doweiko in AIDS 1993, 7; 753-757. Anaemia is present in 35 to 75% of AIDS patients. It is difficult to treat and forces clinicians to lessen the dose of AZT or abort treatment with anti-viral agents.

Pursuant to the goal of inhibiting TNF both α and β forms researchers have focused on it's receptor interaction and mechanism of action.

TNFα and β binds with high affinity to 2 different receptors a 55 kilo-Dalton receptor and a 75 kilo-Dalton receptor. Each receptor produces different pharmacological affects thereby broadening the range of activity of TNF. Significantly there are no TNF receptors on red cells. Indeed, the red cell is an exceptional cell in this respect. The teachings of the present disclosure enable TNF to bind harmlessly to red cells, thereby preventing it's deleterious effects.

The 55 kilo-Dalton TNF receptor has been cloned and sequenced and one is directed to Loetscher H, Pan Y-C E, et al, Cell 61, (1990) 351-359 and also directed to Schall T J et al, Cell 61, (1990) 361-370, incorporated fully herein by reference.

The 75 kilo-Dalton receptor has been cloned and sequenced and one is directed to Smith C A et al (1990) Science 248, 1019-1023 and to Dembic Z et al, 1990, Cytokine 2, 231-237, incorporated fully herein by reference. TNF binding proteins found in the blood stream are now believed to be free TNF receptors shed from cell membranes. Moreover, such natural 'soluble' receptors are believed to control or modify some of the ill effects produced by TNF as suggested by Dan Aderka et al, J. Exp. Med., Vol 175, Feb 92, pp 323-329, and by Endelmann H et al, J. Biol. Chemistry (1989), Vol 264, No 20, July 15, pp 11974-11960. That urinary proteins, TNF receptors, may be biologically useful was still further confirmed by Engelmann H et al, J. Biological Chemistry, Jan 25, pp 1531-1536 (1990) incorporated herein fully by reference.

Biological characterization of TNF-R (TNF-R55 and TNF-R75) shows the receptors to be homogenous and belong to a wider family of similar receptors including NGF-R nerve growth factor receptor, CD40 and CD27, see Peter Vanderbee etal, J. Exp. Med., Vol 176, Oct 1992, 1015-1024.

To lessen the effects of TNF and develop anti-septic shock agents, some workers have tried to administer TNF-R(s) soluble TNF receptors. Studies evaluating monomeric TNF-R both glycosylated and unglycosylated arising from expression in CHO cells and E.Coli respectively, showed monomeric forms of the receptor either glycosylated or unglycosylated to have very low plasma half lives, 3.5 min and 11.6 min for TViα. Rapid renal clearance of the agent appeared to be a major obstacle for monomeric TNF-R as a therapeutic agent.

However, a TNF-R immunoadhesion a chimeric molecule developed by Gennentech demonstrated an improved VS. life with TViβ at 20 mins clearance being mainly liver mediated.

Moreover by replacing the Fab of an antibody with TNF-R segments the affinity of the immunoadhesion agent for TNF is improved. It's chemical efficacy likely to be greater by virtue of the fact that TNF a trimer is normally twice bound to it's receptor therefore preventing dimer adhesion to cell surface receptors which can still occur in the case of singly inhibited TNF molecules.

One is directed to Avi Ashkenazi et al, Proc. Natl. Acad. Sci. USA, Vol 88, pp 10535- 10539, Dec 1991 , for an account of a TNF receptor immunoadhesion incorporated herein fully by reference. This particular construct used a human IGG Fc peptide fragment fused to two TGF-R fragments and was expressed in kidney cells.

A similar hybrid peptide was disclosed by K Peffel et al, J. Exp. Med., Vol 174, Dec 1991, pp 1483-1489 incorporated fully herein by reference. In this example a murine FC + hinge IGG fragment was fused to TNF-R fragments and expressed in CHO cells.

The present invention teaches molecules or molecular machines having an affinity for TNF and human red cells. Thus enabling cells to mop up TNF and causing TNF to adhere to the red cell surface. The disclosure emphasises that TNF is not associated with red cells as a natural phenomenon. The present disclosure teaches an unnatural union between red cells and TNF, by means of novel pharmaceutical protein agents.

A long half life is envisaged for the agents as the red cell surface protects the novel agents from excretion by the kidney. Moreover, the red cell provides steric hinderance preventing a TNF so bound to itself from binding to a TNF-R in another cell.

The present invention derives from PCT 93/00505 and teaches a cytokine receptor, fused to a malaria parasite peptide having affinity for a red cell, or analogue there of, and this provides a molecular machine, a hybrid fusion peptide capable of binding a cytokine (TNFα or β or interferons or interleukins) to the red cell surface thereby inactivating it. The longer half life of such an agent allows greater clinical flexibility in drug administration and allows the agent to remain useful for longer periods.

The present disclosure provides the advantage of a macromolecule capable of dual function TNF binding and red cell adhesion without any separate laboratory procedures on red cells being required. The present disclosure is not confined to TNF or its receptors but teaches the fusion of other cytokine receptors to malaria parasite peptides to produce macromolecules capable of reducing levels of harmful cytokines.

The novel macromelecular agents of the present disclosure bind directly onto red cells in one step, and provide a novel use for modified peptides of the malaria parasite organism.

Of all parasites malaria must be the most damaging and successful. Many millions are infected with 1-2 million deaths per annum. The malaria parasite has evolved from earliest times and attacks not only humans but most varieties of animal. This serious parasite infests red blood cells. Various malaria species infect humans, plasmodium faciparium, and plasmodium vivax being the most important. The life cycle is complex with a short life cycle in the salivary gland of mosquitoes and following inoculation of a human the parasite object is ultimately the red cell. Merozotes bind to the red cell membrane, enter the cytoplasm and multiply. The course of malaria is a variable one and may be characterised by a short acute illness which can bring death in a matter of hours; or a longer more chronic illness associated with debility and anaemia.

Other forms of malaria such as the plasmodium Knowlesi are well researched animal parasites which infects the Rhesus monkey. The preferred location forthe malaria parasite is within the red cells of the infected host and for much of its life span it lives intracellularly protected from the host immune system.

Merozoites are thought to spend but a brief period free in the circulation. Accordingly, considerable research efforts have been expended to discover the means whereby the merozoite forms of the parasite gains attachment and gains entry into the human red cell.

Margaret E Perkins Journal Experimental Medicine 160 September 1984, 788-798 is responsible for formulation of a relationship between the plasmodium falsiparum binding molecule and glycophorin A and B two silao glycoproteins found on the surface of red cells.

More laterally, Holt and Perkins et al American Journal Tropical Medicine Hygiene 1989, p 245-251 disclose species and stain variations of plasmodium falciparum wherein some strains of the organism exhibit preference for sialo glycoproteins glycophorins A, B and C and also demonstrated was the varying requirements for the N-acetyl-neuramic acid residues (NeuNac).

The glycophorin A molecule is a highly glycosylated peptide. Pasvol has suggested that glycophorin binding peptide binds to the region of glycophorin close to the lipid bi-iayer.

Pasvol G et al "Inhibition of Malaria Parasite Invasion of Monoclonical antibodies against glycophorin A correlates with a reduction in red cell membrane deformity." Blood, 74, No. 5, October 1985, 1836-1843.

Debate continues within the literature as to the requirement for siaiic acid on the glycophorin molecule to affect invasion by merozoites.

Some strains of malaria are totally dependent on normally sialated glycophorin A to gain entry into the red cell, whereas other strains seem to be independent of siaiic add. See Mitchell etall 66, No 5, May 1986, 1519-1521. Perkins and Roco in Journal of Immunology 88, Vol 141, 3190-3196, No 9, again stress the importance of siaiic acid where normally sialated glycophorin is necessary to achieve successful binding of merozoite peptides in particular pf200.

For several years a peptide called the glycophorin binding protein was believed to be the primary peptide responsible for binding merozoites to erythrocytes. A gene coding for GBP was isolated by M Ravetch J and Kochian J and disdosed in Science Vol 227, pp 1953- 1596, 29 March 1985 and incorporated herein fully by reference.

GBP 130 is characterised by a tandem repeated sequence coding for a 50 amino add repeating sequence believed to be the site of erythrocyte binding, "A tandem repeated sequence determines the binding domain for an erythrocyte receptor binding protein of plasmodian faldparum". Cell, Vol 44, 689-696, March 14, 1986, Kochan J, Perkins M and Ravetch J. See Figure 2, p691, which also disdoses the full sequence and genetic code of the GBP 130 molecule.

Other workers have challenged the supremacy of the GBP 130 as the primary binding molecule of the malaria merozoite. Oriandi P, Kim Lee Sim etal Molecular and Biochemical Parasitology, 40 (1990) 285-294 "Characterisation of the 175 kilodafton erythrocyte binding antigen of plasmodium falciparum" suggested a different peptide, the EBA 175 molecule, as being responsible for merozoite binding or at least playing some role therein.

The EBA 175 molecule like the GBP 130 molecule has an affinity for the red blood cell surface and binds thereto.

It is known that the EBA 175 molecule has a prediction for olygosaccharides which are found on the surface of the red cell molecule. However, a problem arises in that the EBA 175 molecule does not bind effectively with the malaria merozoite parasite. Therefore, it is thought that the EBA 175 serves a function as a bridge. This disdosure proposes an alternative mechanism in that the EBA 175 molecule is responsible for bringing the merozoite closer to the RBC by binding with the base of the glycophorin A peptide; thus bringing the lipid bi layer of the malaria parasite into approximation with the lipid bilayer of the red cell membrane and thereby allowing the incorporation of the parasite into the erythrocyte itself. This disdosure suggests the merozoite is winched into the RBC cytoplasm.

The genetic sequence and the peptide sequence of EBA 175 was disdosed in J. Cell Biology 11, 1990, Kim Lee Sim, Orlandi P et al "Primary structure of the 175 K plasmodium faldparum erythrocyte binding antigen and identification of a peptide which elicits antibodies that inhibit malaria merozoite invasion" See Cell Biology Vol 111 (1990) p1877-1884, Figure 2 of p 1880 for the sequence of amino acids and DNA sequence.

To further complicate the picture Dagmar Nolte et al described two close relatives of the glycophorin binding peptide 130 molecule which they call GBPH or glycophorin binding peptide homologues. This molecule like the GBP molecule, displays several tandem repeat sequences and a high affinity for the erythrocyte surface membrane surface peptides. It has been proposed by Nolte and co-workers that it is the GBPH molecule and not the GBP molecule is released as an immunogenic decoy to distract the immune system from the real 12 binding peptide the GBPH.

The nucleotide sequence of one form of the peptide GPBH is disdosed by Dagmar Nolte et al in the Journal of Molecular and Biochemical Parasitology, 49, (1991), p 253-264. See Figure 2 of p 257 incorporated herein fully by reference. The peptide sequence is also disclosed.

See also Figure 3 of p 258 the same journal and paper which lists a comparison between GBP 130 and GBPH. Binding and entry of merozoites into RBC's involves several peptides of several alternatives as fail safes for the organism.

The picture is further complicated by other research notably by Peterson Gregory, who proposes PMMSA (Pre major merozoite surface antigen) as being responsible for erythrocyte binding either in this state or following fragmentation into smaller fragments. The genetic sequence and the peptide sequence of the PMMSA molecule is given in the Journal of Molecular and Biochemical Parasitology, 27 (1988), 291-302. See Figure 3 of p294 and 295. Peterson G et al.

Erythrocyte binding using different peptides and surface molecules is exhibited by other species of the malaria parasite in particularthe plasmodium vivax organism. This organism can infect only persons expressing the Duffy marker. The Duffy antigen is a red cell surface marker and is one of many blood group markers and is carried by a percentage of the population.

Persons not expressing Duffy antigens are therefore immune from infection by plasiτiQdium vivax. The plasmodium vivax expresses a Duffy binding receptor molecule P. vivax Duffy receptor was doned and sequenced by Xiangdang Fang and disdosed in Molecular and Biochemical Parasitology, 44(1991) p125-132. See especially Figure 1 of p127 for the genetic sequence and amino add sequence.

Similar to plasmodium vivax is plasmodium Knowiesi which also uses the Duffy antigen. This organism parasitises Rhesus monkeys. Also in the same Journal, same figure, same page, is listed the genetic sequence of plasmodium Knowiesi Duffy receptor molecule which may find a use in the agents of the present disclosure.

When developing therapeutic agents directed against the malaria parasite itself, then it is clearly important to identify the precise molecule responsible for merozoite binding in the clinical context. However, where malaria peptides are to be employed as erythrocyte binding agents more generally, then it is not important to identify the precise peptide the malaria organism uses to effect invasion. Any malaria peptide capable of binding to an erythrocyte surface membrane may have a therapeutic use for other purposes such as the agents of the present disdosure and also segments of such a peptide.

Brief Summary

The present disdosure provides novel hybrid or fusion peptides having a minimum of 2 different peptide components each possessing different functionality. One peptide component will be derived from the malaria parasite or derivative or fragment or variation thereof and possess the ability to bind to a red ceil surface. The other component of the fusion peptide will be a cytokine receptor or derivative or fragment thereof especially the TNF-R75 and 55 (Tumour Necrosis Factor Receptor 75 kilo-Dalton and 55 kilo-Dalton, the IL1-R (interleukin-1 -receptor); the IL6-R (the interleukin 6-receptor); the IL8-R (the interleukin 8 receptor); IL2-R; IL4-R; IL3-R; IL5-R; IL7-R or the LIFR (leukaemia inhibitory factor)-R receptor or the γlFN-R gamma interferon receptor. It is envisaged that the fusion peptide will bind the target peptide to the red cell surface and mop up the free circulating target peptide (cytokine) thereby redudng it's deleterious effects. 14

In the clinical context the novel hybrid fusion peptides of the present disclosure will find therapeutic use in

(a) the prophylaxis and treatment of endotoxic shock (septic shock),

(b) the suppression of hyper-inflammatory states,

(c) as agents for the prevention and treatment of graft versus host disease, autoimmune disease, cerebralmalaria, transplant rejection, pulmonary fibrosis, ulcerative and degenerative diseases,

(d) as agents to treat or delay the onset of AIDS in HIV positive persons or as agents to minimize viral damage in HIV and other viral infections,

(e) as agents to treat cachexia and wasting caused by cancer.

DETAILED DISCLOSURE

The disclosure is best illustrated by reference to the exemplary embodiments described herein after which are non limiting.

EXEMPLARY EMBODIMENT GROUP 1

In this embodiment all or part of the peptide sequence comprising amino acid residues 201- 774 of the GBP 130 (glycophorin binding peptide molecule 130) all or part or substitutional or deletional variations thereof or fragments thereof especially tandem repeats or modified fragments thereof are modified to form hybrid fusion peptide drugs as shown herein below.

The amino add sequence of the glycophorin binding peptide 130 molecule was disdosed by Jarema Kochan et al in Cell Vol.44: 689-696, March 14; 1986. See Figure 2, p691 and is incorporated fully herein by reference. The general formula for the agents is as follows

NH₂— -Ctk-R P COOH or NH₂— P— -CtkR— -COOH a hybrid fusion peptide where Ctk-R represents a cytokine either TNF-R, IL1-R, IL2-R, IL4- R, IL8-R, IL6-R, IL3-R, IL5-R, IL7-R, LIF-R or γlFN-R or fragment thereof and where P represents the GBP130 molecule or fragment thereof, or other malaria derived red cell binding peptide.

Exemplary Embodiment 1(a). 1 of example group 1.

Exemplary embodiment 1(a). 1 is directed to a hybrid protein or fusion peptide capable of binding free TNFα or β to the red cell surface and comprising the fusion of two peptide components - a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan etal in Cell, Vol 44, 689-696, Mar 141986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably, or by linkers to,

- a peptide component derived from all or part of the 55κd Tumour Necrosis Factor Receptor the sequence of which was disdosed by H Loetscher et al in Cell, Vol. 61, 351- 359, April 20 1990, see p353, see Figure 2A for the amino acid sequence and see Figure B for the restriction map, disdosed and incorporated herein fully by reference.

Exemplary embodiment 1(a). 2 of example group 1

Exemplary embodiment 1 (a).2 is directed to a hybrid protein or fusion peptide capable of binding free TNFα or β to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disdosed by Jarema Kochan et al in Cell, Vol 44, 689-696, Mar 14 1986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to,

- a peptide component derived from all or parts of a TNF receptor similar to example 1 (a). 1 but using the amino add sequence disdosed by T J Schall et al in Cell, Vol 61, p 361- 370, April 20 1990, see page 363, Figure 1A for the amino add sequence disdosed and incorporated herein fully by reference.

Exemplary Embodiment 1(a). 3 of example group 1

Exemplary embodiment 1(a). 3 is directed to a hybrid protein or fusion peptide capable of binding free TNFα or β to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan et al in Cell, Vol 44, 689-696, Mar 141986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to,

- a peptide component derived from all or part of the Tumour Necrosis Factor Binding proteins I or II as isolated from human urine and sequenced by Yaran Norphor et al the sequence of which peptides are disdosed in Y Norphor et al EMBO Journal, Vol 9, No 10, pp 3269-3278 (1990) see page 3271 , Figure 1 D and p 3272, Table 1 which sequences are disdosed and incorporated herein fully by reference.

Exemplary Embodiment 1(b). 1 of group 1

Exemplary embodiment 1(b). 1 is directed to a hybrid protein or fusion peptide capable of binding free γlFN gamma interferon to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan et al in Cell, Vol 44, 689-696, Mar 141986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to, - a peptide component derived from all or part of the γlFN receptor molecule the amino add sequence of which was deduced and cloned by Auguet M et al and disclosed in Cell 55(1988), 273-280 and incorporated herein fully by reference.

Exemplary Embodiment 1(b). 2 of group 1

Exemplary embodiment 1(b). 2 is directed to a hybrid protein or fusion peptide capable of binding free γlFN gamma interferon to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan etal in Cell, Vol 44, 689-696, Mar 14 1986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to,

- a peptide component derived from a soluble γlFN receptor as cloned by GENTZ et al and disclosed in GENTZ R etal 1992, Eur. J. Biochem., and disclosed and incorporated herein fully by reference and also as disclosed in p140 of International Review of Experimental Pathology, Vol 34B, see Ozmen, Fountanalkis, Gentz and Garrotta, p 137-1977.

The agents of type example 1(b). 1 and 1(b). 2 may be especially useful in the treatment of G.V.H.D. graft versus host disease.

Exemplary Embodiment 1(c). 1 of group 1

Exemplary embodiment 1(c). 1 is directed to a hybrid protein or fusion peptide capable of binding free IL2 interleukin 2 to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan et al in Cell, Vol 44, 689-696, Mar 14 1986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally 18 to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to,

- a peptide component derived from the high affinity IL2 receptor ie. IL2β as characterized by Bich-Thuy et al 1987, J. Immunology, 139(5), 1550-1556; Dukovich M et al, Nature (London) 327, 518-522; Hatakeyama M etal, 1989, Science 244; 551-556; Robb R J etal, Proc. Natl. Acad. Sci. USA, 84(7) 2002-2006; Saragon H etal, 1990, Proc. Natl. Acad. Sci. USA, 87 (1), 11-15; T Sudo M et al, Proc. Natl. Acad. Schi. USA, 84 (12), 9215-9218 disclosed and incorporated herein fully by reference.

The agents of exemplary embodiment 1(c). 1 may be especially useful to reduce the expression of HIV virus in persons with AIDS.

Exemplary Embodiment 1(d). 1 of examples group 1

Exemplary embodiment 1(d). 1 is directed to a hybrid protein or fusion peptide capable of binding free II-6 interleukin 6 to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan et al in Cell, Vol 44, 689-696, Mar 14 1986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N terminal end by peptide bonds preferably or by linkers to,

- a peptide component comprising or derived from either the high or low affinity IL6 receptor as cloned by Yamasaki K et al, Science (1988), 241 , ρ825-828 and described also by Taga T et al, 1989, Cell 58 (3), 573-581 ; and disdosed and incorporated herein fully by reference.

Exemplary Embodiment 1(e). 1 of group 1

Exemplary embodiment 1(e). 1 is directed to a hybrid protein or fusion peptide capable of binding free IL1 interleukin one to the red cell surface and comprising the fusion of two peptide components

- a peptide component comprising all or part or derived from the IL-1 R interleukin one receptor as disclosed by Sims J E et al (1988), Science 241, 585-589 and disdosed and incorporated herein fully by reference. One is also directed to C J McMahon et al to EMBO Journal Vol 10; No 10' 1991; pp 2821-2832 for details and sequence of a type II IL-1 receptor disdosed and incorporated fully by reference.

Exemplary embodiment 1(f). 1 of group 1

Exemplary embodiment 1(f). 1 is directed to a hybrid protein or fusion peptide capable of binding free LIF leukaemia inhibitory fador to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the leukaemia inhibitory fador receptor as disclosed by Gearing D P et al EMBO. J., 10: 2839-2848 and also disdosed in Geraing D P et al, Polyfunctional cytokines 1L6 and LIF, Wiley Chichester (Ciba Foundation Symposium 167) p245 to p259, see especially 247, 248 and 249, Figure 1, where the amino add sequence of LIF and IL6 are listed and compared, and are disdosed and incorporated herein fully by reference. {Exemplary embodiment 1(g). 1 of group 1

Exemplary embodiment 1(g). 1 is directed to a hybrid protein or fusion peptide capable of binding free Interleukin 3 to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the Interleukin 3 receptor as disdosed by Toshio Kitamura et al in Cell, Vol 66, 1165-1174, Sept 20, 1991, see Figure 1, p1167 incorporated fully herein by reference.

Exemplary embodiment 1(h). 1 of group 1

Exemplary embodiment 1(h). 1 is directed to a hybrid protein or fusion peptide capable of binding free Interleukin 5 to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the Interleukin 5 as disclosed by J Tavernier et al, Cell, Vol 66, Sept 20, pp1175-1184, see Fig 1 , disdosed and incorporated herein fully by reference.

Exemplary embodiment 1(i). 1 of group 1

Exemplary embodiment 1(i). 1 is directed to a hybrid protein or fusion peptide capable of 21 binding free Interleukin 8 to the red cell surface and comprising the fusion of two peptide components

- a peptide component derived from all or part of the GBP 130 molecule (glycophorin binding peptide molecule as disclosed by Jarema Kochan etal in Cell, Vol 44, 689-696, Mar 14 1986, see Figure 2, p 691 and incorporated fully herein by reference fused N terminally to the C terminal end or C terminally to the N ten inal end by peptide bonds preferably or by linkers to,

- a peptide component derived from all or part of the Interleukin 8 receptors type 1 and 2 as disdosed by R Gaylell et al, J. Biological Chemistry, Vol 268, No 10, April 5, pp7283- 7289; 1993, disdosed and incorporated herein fully by reference.

Exemplary Embodiment 1(j). 1 of group 1

Exemplary Embodiment 1(j) is directed to a fusion peptide of a malaria parasite red blood cell binding peptide such as GBP130 fused to the IL4R interleukin 4 receptor all or part. The IL4 receptor was cloned and disclosed by R L Idzerda et al, J, Exp. Med., Vol 171 , Mar. 1990, pp861-873, incorporated fully herein by reference.

EXAMPLE OF AGENTS GROUP 2

The agents of group 2 use the Glycophorin binding peptide homologue molecule for red cell binding.

The glycophorin binding peptide homologue molecule was cloned and disclosed by Dagmar Nolte et al Molecular and Biochem Parasitology, 49(1991) page 253-264. See especially Figure 2, p257 and is incorporated fully herein by reference.

Eχamβ_£ 2(a); 2(b); 2(c); 2(d); 2(e); 2(f); 2(g); 2(h); 2(i);2(j)

The exemplified agents of group 2 are identical in every respect to group 1 except that in place of GBP 130 or segments thereof the malaria RBC binding component is provided by 22 GBPH glycophorin binding peptide homologue as referenced herein above especially peptide fragments comprising amino add residues: residue 70 to 427 inclusive residue 109 to 427 inclusive residue 230 to 268 or any other tandem repeat or polymer thereof of any fragment or species variation or substitution or deletional or inclusional variant thereof.

EXAMPLE OF AGENTS GROUP 3

The agents of group 3 use the EBA 175 erythrocyte binding antigen 175 for red cell binding.

The EBA 175 erythrocyte binding antigen 175 was doned and disdosed by B Kim Lee Sim et al Journal Cell Biology, Vol. Ill, 1990, p1877-1884. See especially Figure 2, p1880 and is incorporated fully herein by reference.

Examete 3(a); 3(b); 3(c); 3(d); 3(e); 3(f); 3(g); 3(h); 3(i), 3(j)

The exemplified agents of group 3 are identical in every respect to group 1 except that in place of GBP 130 or segments thereof the malaria RBC binding component is provided EBA 175 erythrocyte binding antigen 175 espedally peptide fragments comprising amino add residues i residue 20 to 1435 indusive of any other fragment orspedes variation or substitution ordeletional orindusional variant thereof.

EXAMPLE OF AGENTS GROUP 4

The agents of group 4 use the Plasmodium Vivax Duffy Receptor for red cell binding.

The Plasmodium Vivax Duffy receptor was doned and disdosed by Xiangdong Fong et al Molecular Biochemical Parasitology, 44 (1991 ) 125-132. See especially Figure 2, p 127 and is incorporated fully herein by reference.

EχampJfi 4(a); 4(b); 4(c); 4(d); 4(e); 4(f); 4(g); 4(h); 4(i); 4(j)

The exemplified agents of group 4 are identical in every resped to group 1 except that in place of GBP 130 or segments thereof the malaria RBC binding component is provided by

Plasmodium Vivax Duffy Receptor espedally peptide fragments comprising amino add residues; i residue 23 to 1051 inclusive of any other fragment or spedes variation or substitution or deletional or inciusional variant thereof.

EXAMPLEOFAGENTSGROUP5

As for group 1 except the malaria parasite peptides are twice represented.

EXAMPLEOFAGENTSGROUP6

As for group 5 except that 2 different malaria parasite peptides are represented.

EXAMPLEOFAGENTSGROUP7

These agents are as for examples 1, 2, 3, 4, 5 and 6 except the malaria parasite derived component is represented all or in part by i an anti-ideotype Fab fragment ii an antibody fragment binding to red cells in the same way as the malaria parasite components.

EXAMPLES OF MANUFACTURING METHODS

The protein of the present disdosure are fabricated preferably in a stepwise fashion. Many different manufaduring strategies are available for each component any or all of which may 24 be applied in various combinations didated largely by two fadors.

(1) EΞxisting manufaduring fadlities for other produds within a fadory and the cost of alternative strategies.

COST

(2) The minimisation of byproducts which are expensive to produce and eliminate. ie. COST So many methods of manufadure are now available that economics rather than science didates the choice.

Peptide Manufadure

The art continues to provide new techniques for applying the Merrifield synthesis of peptides on a scaled up basis useful for the large scale manufadure of peptides referred to as scale up of solid phase peptide synthesis, SPPS.

The chemical synthesis of even complex peptides such as an entire merozoite peptide falls well within the scope of the art.

In the interests of brevity a full account of Merrifield synthesis will not be given, however, one is direded to:

The Chemical Synthesis of Peptides, John Jones Clarendon Press, 1991; and to G B Fields and R Noble Solid Phase Synthesis Utilising Fluorenylmethoxycarbonyl amino acids. Int.

J Peptides 35 1990 p161-214 as useful points of reference and are incorporated fully herein by reference.

The tandemly repeated architedure of some merozoite peptides render their chemical synthesis more economically viable than other large peptides. Where variations in a peptide sequence are sought ie. substitutional, deletional or insertions of amino adds then it may be very helpful to use Merrifield synthesis for that segment alone.

Newer techniques for multicomponent peptide synthesis permit the simultaneous synthesis of oligo peptide segments in a single run thus redudng time and costs considerably. One is dired to Arpad Fucka et al Int. J Peptide Protein Es 37 1991, 487-493 for details disclosed of a method incorporated fully herein by reference.

The present art continues to provide refinements to old techniques and new tediniques for peptide synthesis either small quantities for research or larger amounts for industrial puφoses. These techniques being familiar to the skilled artisan are disdosed best in standard textbooks and reference texts, accordingly brief reference only will be made to interesting developments which are non limiting.

A recent development involves the use of a new anchoring moiety involving the bonding of (HYCRAM)® (Orpegen GMBh, Czemyring 22, D-6900 Heidelberg FRC) a 4- hydroxylcrotonoyl-amidomethyl grouping bonded to an aminomethyl-polyacrylamide gel via spacer molecules such as B-alanine, or sarcosine or the like. Fmoc-amino adds can be linked to the HYCRAM® by esterification. Also any Boc-amino acid or any Ddz-amino add 3, 5-dimethoxyphenyl-2-propyl-2-oxycarbanyl-amino add salt may be bonded to the HYCRAM® anchor.

Synthesis then proceeds using the Boc-/benzyl, the Ddz-Λ-butyl or the Fmoc-/t-butyl protocols as usual.

Detachment of the peptide from the HYCRAM® support employs palladium tatra-kis (triphynyl-phosphane) a catalyst in a suitable solvent such as 50% (v/v) dimethylsulphoxide 26 with dimethyl formamide' N-methyppyrrolidine, tetrahydrofuran and water. Oxygen tetrahydrofuran must be exduded. Acceptor molecules, morpholine, dimedine or N, N'- dimethylbarbiturate may be added to take up the allylic group.

The Ddz-/t-butly amino acid protedions are easier to cleave using with 1-5% (v/v) trifluroacetic acid in dichloromethane a process taking 10 to 30 minutes or by means of the more environmental friendly acetic add or dioxane containing 1% (w/v) HCL gas.

The other useful protocol is the Fmoc-/t-butyl strategy. Cleavage of F moc can be achieved using 20-50% (v/v) piperidine/dimethyl formamide.

Deprotedion can be monitored in both cases photometrically. The adivation of Boc-; Fmoc-; orDdz-aminoacid derivatives may employ the inexpensive (Dccdidohexylcarbodi- imide. Pre activation using HOBT (N-hydroxybenzotriazole) can be employed to form symmetric anhydrides of proteded amino adds or their esters.

Other activating agents are the Castro Reagent or BOP' Benzotriazole-1-yl-oxy-tris (dimethyl amino) phosphonium hexa flurosphosphate; one is direded to CASTRO b et al (1957) Tetrahedron Lett. 15, 1219; and TBTU the Knorr reagent, Benzotriazole-1-yl-oxy-1, 1, 3-tetramethyluronioum tetrafluoroborate one is direded to Knorr R et al (1989) Tetrahedron Lett. 30, 1927.

Fragment condensation can be achieved using the BOP or the TBTU reagent with HOBT in excess. Proteded peptides must also be in excess, however, solvents and excesses can often be recycled.

It will be appreciated that by blocking incomplete fragment condensations shorter by produds can be discriminated from the desired polypeptide. Using this system high purity 27 polypeptides can be produced.

Monitoring of produdion process will usually involve U.V. absorbtion techniques.

Atypical produdion process involve either the separate synthesis of peptide sequences by their expression in suitable hosts, and their subsequent purification; or chemical synthesis such as on a solid substrate for example by the sequential addition of amion add residues or peptide fragments which are proteded, the protedion of the amino add residues as required and the subsequent reading of the peptide chains with linking agents before removing the peptide chains from the said solid substrates and the final purification by the various means is such as reverse phase chromatography; or any combination of the above.

In the case of some of the exemplary embodiments it may be convenient to manufadure the fusion peptides by means of a fused gene. A fused gene is a genetic sequence which codes both components of the hybrid component molecule. One is direded to Murphy United States Patent 4, 675, 382 for a detailed disdosure of the use of fused genes in the manufadure of hybrid peptides having the components MSH or Melanocyte Stimulating Hormone fused to diphtheria A toxins.

Alternatively peptide fragments may be manufadured by DNA cloning and expression in suitable hosts and recovery with subsequent condensation in vitro.

Generally cloned sequences useful for the produdion of fusion peptides will have the transmembrane domain and the cytoplasmic domain sequence removed.

For a useful general description of DNA cloning and molecular hybridization technology, one is direded to Maniatis et al Moliecular cloning, A Laboratory Manual, Cold Harbour Spring Laboratory (See Second Edition 1989); and to Horvath et al, An Automated DNA synthesizer employing Deoxynucleoide 34 Phosphoramidites, methods in Enzymology 154: 313-326, 1987.

DNA may be made by the chemical synthesis of DNA polymer fragments using phosphotriester, phosphite or phosphoramidite chemistry. For a description of sold phase techniques one is direded to Chemical and Enzymatic Synthesis of Gene Fragments - A Laboratory manual ed H G Gassen and L Lang, Verlag Chemiee, Weinheim 1982; and Gait M J et al Nucleic Acids Research 1982, 10, 6243; Spoat B S et al Tetrahedron Letters, 1980, 21, 719; Matteuci M D et al J. American Chemical Society, 1983, 195, 661; Sinha N D et al Nucleic Acids Research, 1984, 12, 4539 and Matthes H W D et al Embo. Journal, 1984, 3, 801, whose teachings are incorporated herein fully by reference.

Reverse transcriptase techniques may also be used to generate a complimentary cDNA strand by means of the reverse transcription of malaria parasite derived mRNA. Kits are available for this purpose.

The DNA fragments maybe ligated by either blunt-ended orstaggered-ended termini after using restridion enzymes; digestion; filling in a required; and treatment with alkali and phosphatase for protedion and subsequent ligation with suitable ligases.

Appropriate leader sequences may be chosen from the many available.

The cloning of the DNA sequence of the hybrid peptides of this invention may take place in prokaryotes such as E.Coli for example, K12 strain or E Coli B by way of non limiting examples or by means of the polymerase chain reaction.

Subsequent expression of the hybrid peptides may take place in any host cell, induding mammalian host cells. Other useful cells are fungi, yeasts, inseds and prokaryotes. Signals suited to the chosen host cell are chosen as appropriate, in the case of prokaryotes one can chose from a large group induding alkaline phosphatase, pemallinase and the like.

Where prokaryotes such as E Coli for example, are used to express the hybrid peptides, then they are transformed by an expression vedor usually a plasmid sudi as PBR322 into which the DNA encoding the fusion peptide or fragment has been ligated such as plasmid will also feature suitable marker sequences, promoters, and Shine-Dalgarno sequences may be chosen as appropriate.

A prokaryote host such as E Coli may be transformed by treatment using a solution of CaCI₂ as described by Cohen et al PNAS 1973, £2, 2110 or by treatment with a solution comprising a mixture of RbCI, MnCI₂, potassium acetate and glycerol and then subsequently with 3 -[N-morpholino] - propene-sulphonic add and, RbCI and glycerol. One is described to "DNA Cloning" Vol II D M Gover ed, IRL press Ltd 1985 for a description of transforming techniques.

Where insed cells such as Lepidoptera cells are the chosen expression host a suitable vedor would be Bacuiovirus. Such a system would contain the target peptide encoding sequence linked to a bacuiovirus promoter within a shuttle vedor with sufficient bacuiovirus DNA flanking the target peptide encoding sequence to permit recombination. One is direded to Summers et al, TAES Bull (Texas Agricultural Experimental Station Bulletin) NR 1555 May 1987. One is also direded to Smithklein (WO/US/89/05550). Insed larvae can also be direded to PCT/WO/88/0200030 Miller et al. Other useful inseds are Drosophila melanogasteric, and the like.

Where plant cells are the chosen host expression cells, the cowpea plant provides a suitable expression system. One is direded to the system developed by the Agriculture Genetics Company of Cambridge, UK, employing techniques involving the use of the cowpea mosaic virus (CPMV). A general protocol for the cloning of foreign genes in plants (tomatoe) and the like may be obtained by consulting HORSC R B et al Science 227, 1229- 31.

Alternatively where the chosen host is a yeast such as Saccharomyces cerevisiae the plasmid YRp7 as the expression vedor may be used. One is direded to Stinchcomb et al Nature 282, 39, (1979), Kingsman et al, G7; 141 (1979); Tschemper et al, Gene 10; 1975 (1980).

A wide choice of promoters is available for use in yeast cell expression systems and indude byway on non limiting examples 3-phosphoglycerate kinase and one is direded to Hitzman et al J. Biol. Chem. 255 2073 (1980); also enolase, glyceraldehyde-3-phosphate dehydroginase, hexokinase, pyruvate decarboxylase, phosphofrudokinase, glucose-6- phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triose phosphate isomerase, phospho glucose isomerase and glucokinaise being glycolytic enzymes and one is direded to Hess et al J. Adv. Enzyme Reg. 7, 149 (1968) and to Holland Biochemistry 17, 4900 91978.

Other promoters suitable for yeast expression systems indude the promoter regions for alcohol dehydrogenase 2, 100 cytochrome C, acid phosphatase, also mettallothioneins, glycoraldehyde-3-phosphate dehydrogenase and others one is direded to Hitzman R et al European patent Publication No. 73, 657A.

Where mammalian cells are the chosen hosts for expression, these cells may be grown in vitro in tissue culture or suitable bioreadors or in vivo in animals.

Vedors useful for mammalian cells host systems involve the use of DNA derived from animal viruses such as SV40 virus; retroviruses such as RSV, MMTV, MOMLV, 31 bacuiovirus, Vaccinovirus, Andeovirus, polyoma or bovine papilloma virus.

Promoters suitable for mammalian cells systems may be chosen from the many available. One is direded to Friers et al Nature 273; 113 (1987) and Greenway P J et al Gene 18, 353-360 (1982) and Okayamah Mol Cell Biol. 3, 280 1 1983, by way of example.

Additionally suitable enhancers may be chosen from the many available. One is direded to Laimins L et al PNAS 78, 993 (1981) and Lusky M L et al MO. Cell Bio. 3, 1108 (1983) and Banerji J L et al Cel. 33, 729 (1983) and Osboume T F et al Mol. Cel. Bio. 4, 1293 (1984).

For as description of some available seledion techniques one is direded to Southern et al J. Molec. Appil. Genet. 1, 327 (1982) and to Mulligan et al Science 209; 1422 (1980) and to Sugden et al Mol. Cel. Biol. 5, 410-413 (1985).

Some techniques useful for the introdudion of the expression vedor into the host cell involve protoplast fusion, calcium phosphate precipitation, eledroporation, and other techniques.

Mammalian host cells suitable for the expression of fragments of or in some cases the entire fusion peptides may now be chosen from the large number now available such as VERO or CHO-K1, a myloma cell line.

Other suitable eukaryotic host cells indude COS cells, human embryonic kidney cells, mouse plasmoacytoma cells, mouse sertoli cells, baby hamster kidney cells (BHK cells), Chinese hamster ovary cells - DKFR(CHO), monkey kidney cells, African green monkey kidney cells, human cervical carcinoma cells (HELA cells), canine kidney cells, Buffalo rat liver cells, human lung cells, human liver ceils and mouse mammary tumour cells, byway 32 of non limiting examples.

It will be appreciated that the chosen host cells will preferably express the minimum levels proteases within their cytoplasm. It will also be appreciated that amino add sequence variations of the peptide sequences involved may be insertions, substitutional or deletional variations involving single amino add residues or peptide fragments.

The purpose of such variations may be to increase the affinity of the components, to improve stability, to reduce the cost preparation or to increase the half life, or to lessen the severity of side effeds sudi as atopic readions. The final form of the agents of the present disclosures may involve any combination of substitutions, deletion or insertion of amino add sequences, provided the binding ability of the epitopes or peptide sequence are retained.

It will be appreciated that also induded in the present disclosure are glycosylation variations ie. variants completely unglycolated, variants having glycosyltaβd amino adds other than those glycosylated in the natural peptides or variants having a greater number of amino adds residues glycosylated or fewer glycosylated residues or residues glycolated by oiigosaccharides other than those oligosaccharides usually associated with the said sequences.

Following their expression by the host cell, the peptides are recovered and purified by means known to the ordinary skilled artisan.

Such methods may include add extradion, ethanol precipitation using ammonium sulphate, anion or cation exchange chromatography phosphocellulose chromatography, immunoaffinity, chromatography hydroxyappetite chromatography and reverse phase chromatography. Generally purification and processing involves four stages:

(1 ) extraction of peptides from host cell

(2) initial purification

(3) final purification

(4) produdion polishing

Extradion may be accomplished using sonication techniques or solid shear techniques - on a small scale.

Lysozyme based techniques are expensive. More usually in the case of baderial hosts homogenizers or liquid shear techniques are employed.

Other useful techniques involve osmotic shock, freezing and thawing or alkali homogenisation.

In the case of where a produd is expressed as an indusion body cell paste may be solubilised by solvents such as 8M-guanidinium.

Centrifugation provides the removal cellular debris, and continuous flow centrifuges are preferred for large scale operations. As an alternative to centrifugation cross flow filtration using flat to tubular membranes and high shear forces may provide a useful alternative to centrifugation.

Initial purification involves mainly the removal of excess water and produd concentration.

Precipitation using ammonium sulphate, organic solvents, polyethylene glycol or other polymers can be used to accomplish this step; with the addition of some variety of chromatography usually absorptive chromatography techniques employing ion exchange, hydrophobic or bioaffinity interadions; followed by washing and desorption; chromatography is not restrided to columns but may take place in membranes or even in spirally wounded cartridges.

In cases where peptide fragments have been expressed as inclusion bodies an additional step of 'refolding' is required. Because of low yields after refolding inclusion body produdions is often uneconomical. However, two approaches are pradised to refold peptides into the natural or desired three dimensional state the empirical approach and the rationalist approach.

In the empirical approach multiple solvents are applied and an optimum strategy is determined using phase diagrams as disdosed by Ahmed and Biglow 1979 J. Mol. Biol. 131. 6097-617.

The rationalist approach seeks to produce conditions favouring the native state while at the same time keeping intermediates in solution.

A problem may arise in connection with disulphide bridges which may form in non-native configurations. A way around this problem is to oxidize disulphides under denaturing conditions, using gel filtration remove covalent aggregates and thereafter dilute the produd in a non denaturing buffer. The peptide which collapses into an amorphous tangle often rearranges itself into the native form.

Highly resolving chromatography is the preferred technique for final purification. For large scale applications columns are preferred and techniques such as gel filtration, ion exchange, hydrophobic interadion or affinity chromatography may be used alone or in combination as didated by economies of scale. 35

Gel filtration is best suited to small batch volumes and suffers from the disadvantage of slow speed.

Ion exchange chromatography techniques are very useful in early purification stages and can deal with large volumes at great speed, producing yields of high resolution.

Hydrophobic interadion chromatography provides both high resolution and high speed even at large batch volumes.

Bio affinity chromatography produces the highest resolution, at high speed, but batch size may require curtailment. This technique is an ideal late stage technique.

The increasing availability of monodonal antibodies at lower prices has led to greater use of bio affinity chromatographic techniques.

A wide choice of chromatographic matrices is now available on the market suitable for large scale use.

Particle size is decreasing from the 90μm of traditional gels to approximately 40μm for newer gels such as Sepharose HR®, Suphacryl HR®, Superdex® (Pharmacia - LKB) or Fradogel® (Toso-Haas).

Other polymeric partides are Superose® (Pharmacia - LKB) or the TSKPW® varieties manufadured by (Toso Haas, Philadelphia USA), providing very low particle size.

It will be appreciated that the process of chromatography involves the choice and development of a strategy containing one or more steps ie. high resolution single step or a multistep procedure the final choice to be determined by (1) the chosen peptide produdion process which determines the form of the starting material to be purified

(2) cost

Usually the first chromatography column will involve large diameter packings circa 100μm, which are often chosen so that they can be resanitized by sodium hydroxide to reduce costs. Low resolution steps to be followed by higher resolution steps until the desired produd purity is obtained.

Step One Hydrophobic interadion chromatography at low ionic strength. Purpose to absorb proteinases. Target peptide not absorbed and colleded. Alternative use proteinase inhibitors.

Step Two Re-run through h.l.c column adding salts to bind the target peptide to the h.l.c column. The objedive is volume reduction. Alternatively employ ultra filtration as described. Use a step gradient to elute the target peptide.

Step Three A step gradient to a low ionic strength buffer will remove remaining salts. Alternatively employ polyethyleneimine precipitation, centrifugation and diafiltration.

In the case of therapeutic peptides such as the agents of this disdosure where administration to a human is considered then the step of produce polishing is vital.

Produd polishing involves the removal of polymers of the produd and other pyrogens.

Techniques for produd polishing involve additional gel filtration with or without a buffer exchange step; treatment with alhydrogel (aluminium hydroxide) ortreatment with specific lecithins or anion exchanges. EXAMPLE OF USE OF AGENTS IN TESTING KITS

A sample of patients blood 50ml is colleded in a suitable container. It is desired to measure free TNFα or levels of circulating cytokines to determine elevation of these levels implying say endotoxic shock.

1mg of the hybrid fusion peptides of group 1a1, 1a2 or2a1 or 3a or 4a or 5a are mixed with 10ml of blood to be assayed. Thereafter the antibodies direded against the complex TNF- TNF-R-malaria parasite peptide are added. These antibodies may be radiolabelled or labelled with luminescent groups or labelled by other means. The blood sample is then spun and rediluted, re-spun and rediiuted. Thereafter the sample is put through an automated counter. The agents attach individual molecules of TNF to red cells and permit visualization and quantification of very small amounts, molecule by molecule of TNF on a red cell with very few laboratory steps. Moreover, as red cells lack TNF receptors the procedure should be accurate and permit measurement of very small amounts of TNF. As for TNF other cytokines may be assayed in the same way.

38 EXAMPLES OF AMINO ACID SEQUENCES

The invention will be further illustrated by an amino add sequence listing of some of the exemplary embodiments, which are intended to be illustrative but not limiting. It will be appreciated by the skilled artisan that the sequence listed here under are but a few of the many possible variations in accordance with the teachings of the present disclosure, these other variations being obvious to the artisan of ordinary skill are accordingly omitted in the interest of brevity. It will also be appreciated that in the following sequence listings the signal and transmembrane and cytoplasmic domains of the disdosed peptides are deleted. However, they may be included to fadlitate expression or extend half life if desired, in accordance with the teachings of the present disdosure.

It will also be appreciated that not all the cytokine receptor sequences can be listed and are excluded in the interest of brevity. Those cytokine receptor sequences not listed are well known to the skilled artisan and freely available in referenced texts and literature of the art. The substitution of such unlisted receptor sequences involves no intensive steps and falls within the skill of the ordinary skilled artisan.

A Examples of TNF-receptor malaria peptide fusion peptide. In the following examples the TNF receptor sequence is in accordance with H Loetscher et al Cell, Vol.61, 351-359, April 20; 1990, p353, Fig.2A, the malaria parasite components as referenced herein before,

A1 NH--TNF-R - GBP 130-COOH

For an example of this peptide one is direded to the document of formal sequence listings.

A2 NH,-TNF-R - GBPH-COOH (glycophorin binding peptide homologue)

A3 H₂J F-R - EBA 175-CQQH

A4 m₂ TNF - PI. Vivax Duffy R - COOH

A5 NH--TNF-R - GBP 130-COOH

An example of a polymer of an amino add repeat sequence. For an example of this peptide one is direded to the document of formal sequence listings.

A6 NH.-TNF-R - GBPH-COOH (glycophorin binding peptide homologue)

An example of a polymer of an amino add repeat sequence.

B1 Example of one fusion peptideformed bythefusion ofTNF-R tumour necrosis fador receptor with a malaria red cell binding peptide GBP130 the tumour necrosis fador receptor amino add sequence as disdosed by Y Norphor et al, EMBO Journal Vol 9; No. 10; 40 pp3269-3278 (1990), see page 3271.

B1 NH. TNFR - GBP130-COOH

C Example of one fusion peptide formed by fusion of TBPI tumour necrosis binding protein 1 with a malaria red cell binding peptide GBP130 already referenced herein TBPI being in accordance with Y NORPHOR et al EMBO Journal; Vol 9; No 10; PP3269-3278 (1990) see page 3271 Fif ID and p3272.

C1 NH_: - TBPI - GBP130 - COOH

D1 Example of TBPII - GBP130 fusion peptide where TBPII is the tumour necrosis binding peptide type II as disdosed by NORPHOR et al EMBO. J. Vol 9; No 10; pp3269-3278 (1990) Fig 10 of p3271 and p3272 incorporated fully herein by reference.

D1 NH. - TBPII - GBP130 - COOH

D2 Example of a fusion peptide where the TNFR sequence is in accordance with all or part that disdosed by C A Smith and one is direded to Science, Vol. 248; 25 May 1990, P. 1021.

D2 NH. - TNFR - GBP 130 - COOH

For an example of this peptide one is direded to the document of formal sequence listings. E Example of γlFN-R-GBP130 fusion peptide where γlFN-R is the γlFN gamma interferon receptor as disdosed by Auguet M et al Cell 55 (1988) pp273-280; Od 21 1988; see Fig 2.

E1 NH. - γlFN-R - GBP 130 - COOH

F Example of IL-1 R-GBP 130 fusion protein where IL-1 is the type II receptor cloned and described by C J M Mahon et al EMBO Journal; Vol 10; No 10, pp2821-2832 (1991), see Fig 3.

F1 NH. - IL-1R type II - GBP 130 - COOH

G Example of IL-1 R type I - GBP 130 sequence of IL-IR type 1 as listed by M:Mahon et al EMBO J.; Vol 10; No 10; pp2821-2832 (1991); Fig 3.

G1 NH.-IL1R type 1 - GBP130 - COOH

H EΞxample of IL2-R - GBP 130 fusion proteins - COOH

H1 In this example the IL2-R molecule is in accordance with part of the IL2 molecule disdosed by T Nikaido et al, Nature, Vol 311, 18 Od 1984, pp631 to P.635 incorporated fully herein by reference. H1 t_₂ - IL2-R - GBP 130 - COOH

For an example of this peptide one is directed to the document of formal sequence listings.

H2 In this example the IL2 receptor molecule is in accordance with part of that molecule as disdosed by D Cosman et al, Nature, Vol 312; 20/27, December 1984, pp768- 771 especially page 770 incorporated fully herein by reference.

H2 NH. - IL2-R - GPB 130 - COOH

H3 In this example the IL2 receptor is formed by the IL2-R β chain as disdosed by Masanori Hatakeyama et al and one is direded to Science, Vol. 244, 5 May 1989, pp 551-556 see especially page 552 figure 1B.

H3 N . - IL2-R - GBP 130 - COOH

I Example of IL-3R-GBP130 fusion protein the IL-3R amino acid sequence is disdosed by Toshio Kitamura et al Cell, Vol 60, 1165-1174, Sept 20, 1991 and incorporated fully herein by reference.

II m₂ - IL-3R - GBP 13Q - COOH

J Example of IL4-R-GPB 130 fusion protein where the amino add sequence of IL4-R interleukin 4 receptor is in accordance with part of that IL4R sequence disdosed by RL Idzerda etal and one is direded to J. Exp. Med., Vol. 171: Mar 1990, pp861-873 especially to page 864 incorportated fully herein by reference. J MH₂ - IL4-R - GBP 13Q - CQOH

K EΞxample of IL-5R - GBP130 fusion protein where the amino acid sequence of IL-5R is all or part of that sequence provided by Jan Tavernier et al, Cell, Vol 66, 1175- 1184, Sept 20, 1991.

K1 NH. - IL-5R - GBP 130 - COOH

L [Example of IL-6R - GBP 130 fusion protein where the amino acid sequence of IL-6R is given by Katsuhiko Yamasaki et al Science, Vol 241 ; 12 Aug 1988; p825-827, see Fig 4, p826.

L1 i₂-IL-6R - GBP 13Q - CQQH

M Example of IL-8R-GBP 130 fusion peptide where the sequences of IL-9R type 1 and type II ar according to Richard Gayle III et al J. of Biological Chemistry, Vol 268, No 10, Apr 5, pp 7283-7289, see Fig 1.

M1 m₂ - IL-8 R type 1 - GBP 13Q - CQQH

M2 NH_: - IL-8R type 2 - GBP 130 - COOH

N Example of LIF-R-GBP 130 fusion protein where the LIF-R amino add sequence is in accordance with Gearing et al.

N1 NH. - LIF-R - GBP 130 - COOH

In the preceeding examples of fusion peptides it will be appredated that the signal and transmembrane and cytoplasmic domains have been deleted preserving only the fundional extracellular domains. These deleted segments may be reintroduced or other peptide segments inserted without departing from the scope or spirt of this disdosure.

The Patent Cooperative Treaty

Title: Pharmaceutical Composition

Amino Acid Sequence Listing

Type: Hyptothetical

Agent: Dr J G Holdcroft

Agent's Reference: jgir.ec: 10588

Inventor: K F PRENDERGAST

Service Address: Graham Watt & Co Riverhead, Sevenoaks, KENT TN132BN

NH_;-TNF-R - GBP 130-COOH

NH₂ - He Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Asn Asn Ser He Cys Cys Thr Lys Cys His Lys Gly Thr Tyr Leu Tyr Asn Asp Cys Pro Gly Pro Gly Gin Asp Thr Asp Cys Arg Glu Cys Glu Ser Gly Ser Phe Thr Ala Ser Glu Asn His Leu Arg His Cys Leu Ser Cys Ser Lys Cys Arg Lys Glu Met Gly Gin Val Glu He Ser Ser Cys Thr Val Asp Arg Asp Thr Val Cys Gly Cys Arg Lys Asn Gin Tyr Arg His Tyr Trp Ser Glu Asn Leu Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin Glu Lys Gin Asn Thr Val Cys Thr Cys His Ala Gly Phe Phe Leu Arg Glu Asn Glu Cys Val Ser Cys Ser Asn Cys Lys Lys Ser Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He Glu Asn Val Lys Gly Thr Glu Asp Ser Gly Thr Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys lie Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

NH.-TNF-R - GBPH-COOH (glycophorin binding peptide homologue)

NH₂ - He Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Asn Asn Ser He Cys Cys Thr Lys Cys His Lys Gly Thr Tyr Leu Tyr Asn Asp Cys Pro Gly Pro Gly Gin Asp Thr Asp Cys Arg Glu Cys Glu Ser Gly Ser Phe Thr Ala Ser Glu Asn His Leu Arg His Cys Leu Ser Cys Ser Lys Cys Arg Lys Glu Met Gly Gin Val Glu He Ser Ser Cys Thr Val Asp Arg Asp Thr Val Cys Gly Cys Arg Lys Asn Gin Tyr Arg His Tyr Trp Ser Glu Asn Leu Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin Glu Lys Gin Asn Thr Val Cys Thr Cys His Ala Gly Phe Phe Leu Arg Glu Asn Glu Cys Val Ser Cys Ser Asn Cys Lys Lys Ser Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He Glu Asn Val Lys Gly Thr Glu Asp Ser Gly Thr Ser Gin Tyr Lys Gin Ala Ala Asp Tyr 199 Ser Phe Arg Glu Ser Arg Val Leu Ala Glu Gly Lys Ser Thr Ser Lys Lys Asn Ala Lys

219 Thr Ala Leu Arg Lys Thr Lys Gin Thr Thr Leu Th*r Ser Ala Asp Pro Glu Gly Gin He

239 Met Lys Ala Trp Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Asn Val Leu Tyr Gin He

259 Leu Asn Asn Thr Asp Pro Asn Asp Glu Leu Glu Th*r Ser Ala Asp Pro Glu Gly Gin

278 He Met Lys Ala Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Asn Val Leu Tyr Gin He

299 Leu Asn Asn Thr Asp Pro Asn Asp Glu Val Glu Se*r Ser Ala Asp Pro Glu Gly Gin He

319 Met Lys Ala Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu

340 Asn Asn Thr Asp Pro Asn Asp Glu Leu Glu Th*r Ser Ala Asp Pro Glu Gly Glή He Met

360 Lys Ala Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu Asn

381 His Thr Asp Ser Ser Glu Val Glu Th*r Ser Ala Asp Pro Glu Gly Gin He Met Lys Ala

401 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu Asn His Thr

422 Asp Ser Ser Glu Val Glu Th*r Ser Ala Asp Pro Glu Gly Gin He Met Lys Ala Tyr Ala

442 Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu Asn Asn Thr Asp

462 Pro Asn Asp Glu Leu Glu Th*r Ser Ala Asp Pro Glu Gly Gin He Met Lys Ala Tyr Ala

482 Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu Asn Asn Thr Asp

502 Pro Asn Asp Glu Leu Glu Th^*r Ser Ala Asp Pro Glu Gly Gin He Met Lys Ala Tyr Ala

522 Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He Leu Asn Asn Thr Asp

542 Pro Asn Asp Glu Ser Ser-COOH

A3 1₂-TNF-R - EB 175-CQQH

NH₂ - lie Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg

20 Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Asn Asn Ser He Cys Cys Thr

40 Lys Cys His Lys Gly Thr Tyr Leu Tyr Asn Asp Cys Pro Gly Pro Gly Gin Asp Thr Asp

60 Cys Arg Glu Cys Glu Ser Gly Ser Phe Thr Ala Ser Glu Asn His Leu Arg His Cys Leu

80 Ser Cys Ser Lys Cys Arg Lys Glu Met Gly Gin Val Glu He Ser Ser Cys Thr Val Asp

100 Arg Asp Thr Val Cys Gly Cys Arg Lys Asn Gin Tyr Arg His Tyr Trp Ser Glu Asn Leu

120 Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin

139 Glu Lys Gin Asn Thr Val Cys Thr Cys His Ala Gly Phe Phe Leu Arg Glu Asn Glu Cys

159 Val Ser Cys Ser Asn Cys Lys Lys Ser Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He Glu Asn Val Lys Gly Thr Glu Asp Ser Gly Thr Ala Arg Asn Glu Tyr Asp He Lys Glu Asn Glu Lys Phe Leu Asp Val Tyr Lys Glu Lys Phe Asn Glu Leu Asp Lys Lys Lys Tyr Gly Asn Val Gin Lys Thr Asp Lys Lys He Phe Thr Phe lie Glu Asn Lys Leu Asp He Leu Asn Asn Ser Lys Phe Asn Lys Arg Trp Lys Ser Tyr Gly Thr Pro Asp Asn lie Asp Lys Asn Met Ser Leu He Asn Lys His Asn Asn Glu Glu Met Phe Asn Asn Asn Tyr Gin Ser Phe Leu Ser Thr Ser Ser Leu He Lys Gin Asn Lys Tyr Val Pro He Asn Ala Val Arg Val Ser Arg He Leu Ser Phe Leu Asp Ser Arg He Asn Asn Gly Arg Asn Thr Ser Ser Asn Asn Glu Val Leu Ser Asn Cys Arg Glu Lys Arg Lys Gly Met Lys Trp Asp Cys Lys Lys Lys Asn Asp Arg Ser Asn Tyr Val Cys He Pro Asp Arg Arg He Gin Leu Cys He Val Asn Leu Ser lie lie Lys Thr Tyr Thr Lys Glu Thr Met Lys Asp His Phe He Glu Ala Ser Lys Lys Glu Ser Gin Leu Leu Leu Lys Lys Asn Asp Asn Lys Tyr Asn Ser Lys Phe Cys Asn Asp Leu Lys Asn Ser Phe Leu Asp Tyr Gly'His Leu Ala Met Gly Asn Asp Met Asp Phe Gly Gly Tyr Ser Thr Lys Ala Glu Asn Lys He Gin Glu Val Phe Lys Gly Ala His Gly Glu He Ser Glu His Lys He Lys Asn Phe Arg Lys Glu Trp Trp Asn Glu Phe Arg Glu Lys Leu Trp Glu Ala Met Leu Ser Glu His Lys Asn Asn He Asn Asn Cys Lys Asn He Pro Gin Glu Glu Leu Gin lie Thr Gin Trp He Lys Glu Trp His Gly Glu Phe Leu Leu Glu Arg Asp Asn Arg Ser Lys Leu Pro Lys Ser Lys Cys Lys Asn Asn Thr Leu Tyr Glu Ala Cys Glu Lys Glu Cys He Asp Pro Cys Met Lys Tyr Arg Asp Trp He He Arg Ser Lys Phe Glu Trp His Thr Leu Ser Lys Glu Tyr Glu Thr Gin Lys Val Pro Lys Glu Asn Ala Glu Asn Tyr Leu He Lys He Ser Glu Asn Lys Asn Asp Ala Lys Val Ser Leu Leu Leu Asn Asn Cys Asp Ala Glu Tyr Ser Lys Tyr Cys Asp Cys Lys His Thr Thr Thr Leu Val Lys Ser Val Leu Asn Gly Asn Asp Asn Thr He Lys Glu Lys Arg Glu His He Asp Leu Asp Asp Phe Ser Lys Phe Gly Cys Asp Lys Asn Ser Val Asp Thr Asn Thr Lys Val Trp Glu Cys Lys Asn Pro Tyr He Leu Ser Thr Lys Asp Val Cys Val Pro Pro Arg Arg Gin Glu Leu Cys Leu Gly Asn He Asp Arg He Tyr Asp Lys Asn Leu Leu Met He Lys Glu His He Leu Ala He Ala He Tyr Glu Ser Arg He Leu Lys Arg Lys Tyr Lys Asn Lys Asp Asp Lys Glu Val Cys Lys He He Asn Lys Thr Phe Ala Asp He Arg Asp He He Gly Gly Thr Asp Tyr Tφ Asn Asp Leu Ser Asn Arg Lys Leu Val Gly Lys He Asn Thr Asn Ser Lys Tyr Val His Arg Asn Lys Lys Asn Asp Lys Leu Phe Arg Asp Glu Trp Trp 764 Lys Val He Lys Lys Asp Val Trp Asn Val He Ser Trp Val Phe Lys Asp Lys Thr Val Cys

785 Lys Glu Asp Asp He Glu Asn He Pro Gin Phe Phe Arg Trp Phe Ser Glu Trp Gly Asp

805 Asp Tyr Cys Gin Asp Lys Thr Lys Met He Glu Thr Leu Lys Val Glu Cys Lys Glu Lys

825 Pro Cys Glu Asp Asp Asn Cys Lys Ser Lys Cys Asn Ser Tyr Lys Glu Trp He Ser Lys

845 Lys Lys Glu Glu Tyr Asn Lys Gin Ala Lys Gin Tyr Gin Glu Tyr Gin Lys Gly Asn Asn

865 Tyr Lys Met Tyr Ser Glu Phe Lys Ser He Lys Pro Glu Val Tyr Leu Lys Lys Tyr Ser Glu

886 Lys Cys Ser Asn Leu Asn Phe Glu Asp Glu Phe Lys Glu Glu Leu His Ser Asp Tyr

905 Lys Asn Lys Cys Thr Met Cys Pro Glu Val Lys Asp Val Pro He Ser He He Arg Asn Asn

926 Glu Gin Thr Ser Gin Glu Ala Val Pro Glu Glu Asn Thr Glu He Ala His Arg Thr Glu Thr

947 Pro Ser He Ser Glu Gly Pro Lys Gly Asn Glu Gin Lys Glu Arg Asp Asp Asp Ser Leu

967 Ser Lys He Ser Val Ser Pro Glu Asn Ser Arg Pro Glu Thr Asp Ala Lys Asp Thr Ser

987 Asn Leu Leu Lys Leu Lys Gly Asp Val Asp He Ser Met Pro Lys Ala Val He Gly Ser

1007 Ser Pro Asn Asp Asn He Asn Val Thr Glu Gin Gly Asp Asn He Ser Gly Val Asn Ser

1027 Lys Pro Leu Ser Asp Asp Val Arg Pro Asp Lys Lys Glu Leu Glu Asp Gin Asn Ser Asp

1047 Glu Ser Glu Glu Thr Val Val Asn His He Ser Lys Ser Pro Ser He Asn Asn Gly Asp Asp 1068 Ser Gly Ser Gly Ser Ala Thr Val Ser Glu Ser Ser Ser Ser Asn Thr Gly Leu Ser He 1088 Asp Asp Asp Arg Asn Gly Asp Thr Phe Val Arg Thr Gin Asp Thr Ala Asn Thr Glu Asp 1108 Val He Arg Lys Glu Asn Ala Asp Lys Asp Glu Asp Glu Lys Gly Ala Asp Glu Glu Arg

1028 His Ser Thr Ser Glu Ser Leu Ser Ser Pro Glu Glu Lys Met Leu Thr Asp Asn Glu Gly

1048 Gly Asn Ser Leu Asn His Glu Glu Val Lys Glu His Thr Ser Asn Ser Asp Asn Val Gin 1068 G'n Ser Gly Gly lie Val Asn Met Asn Val Glu Lys Glu Leu Lys Asp Thr Leu Glu Asn 1088 Pro Ser Ser Ser Leu Asp Glu Gly Lys Ala His Glu Glu Leu Ser Glu Pro Asn Leu Ser 1108 Ser Asp Gin Asp Met Ser Asn Thr Pro Gly Pro Leu Asp Asn Thr Ser Glu Glu Thr Thr 1128 Glu Arg He Ser Asn Asn Glu Tyr Lys Val Asn Glu Arg Glu Asp Glu Arg Thr Leu Thr 1148 Lys Glu Tyr Glu Asp He Val Leu Lys Ser His Met Asn Arg Glu Ser Asp Asp Gly Glu 1168 Leu Tyr Asp Glu Asn Ser Asp Leu Ser Thr Val Asn Asp Glu Ser Glu Asp Ala Glu Ala 1188 Lys Met Lys Gly Asn Asp Thr Ser Glu Met Ser His Asn Ser Ser Gin His He Glu Ser 1208 Asp Gin Gin Lys Asn Asp Met Lys Thr Val Gly Asp Leu Gly Thr Thr His Val Gin Asn 1228 Glu He Ser Val Pro Val Thr Gly Glu He Asp Glu Lys Leu Arg Glu Ser Lys Glu Ser Lys 1249 He His Lys Ala Glu Glu Glu Arg Leu Ser His Thr Asp He His Lys He Asn Pro Glu Asp

1270 Arg Asn Ser Asn Thr Leu His Leu Lys Asp He Arg Asn Glu Glu Asn Glu Arg His Leu

1290 Thr Asn Gin Asn He Asn He Ser Gin Glu Arg Asp Leu Gin Lys His Gly Phe His Thr

1310 Met Asn Asn Leu His Gly Asp Gly Val Ser Glu Arg Ser Gin He Asn His Ser His His

1330 Gly Asn Arg Gin Asp Arg Gly Gly Asn Ser Gly Asn Val Leu Asn Met Arg Ser Asn Asn

1350 Asn Asn Phe Asn Asn He Pro Ser Arg Tyr Asn Leu Tyr Asp Lys Lys Leu Asp Leu Asp

1370 Leu Tyr Glu Asn Arg Asn Asp Ser Thr Thr Lys Glu Leu He Lys Lys Leu Ala Glu He

1390 Asn Lys Cys Glu Asn Glu He Ser Val Lys Tyr Cys Asp His Met He His Glu Glu He Pro

1411 Leu Lys Thr Cys Thr Lys Glu Lys Thr Arg Asn Leu Cys Cys Ala Val Ser Asp Tyr Cys

1431 Met Ser Tyr Phe Thr Tyr Asp Ser Glu Glu Tyr Tyr Asn Cys Thr Lys Arg Glu Phe Asp

1451 Asp Pro Ser Tyr Thr Cys Phe Arg Lys Glu Ala Phe Ser Ser Met He Phe Lys Phe Leu

1471 He Thr Asn Lys He Tyr Tyr Tyr Phe Tyr Thr Tyr Lys Thr Ala Lys Val Thr He Lys Lys

1492 He Asn Phe Ser Leu He Phe Phe Phe Phe Phe Ser Phe-COOH

A4 NH. TNF - PI. Vivax Duffy R - COOH

NH₂ - He Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg

120 Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin

159 Val Ser Cys Ser Asn Cys Lys Lys Ser Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He

179 Glu Asn Val Lys Gly Thr Glu Asp Ser Gly Thr Lys Asp Asp Phe Ser He Thr Leu He

199 Asn Tyr His Glu Gly Lys Lys Tyr Leu He He Leu Lys Arg Lys Leu Glu Lys Ala Asn Asn

220 Arg Asp Val Cys Asn Phe Phe Leu His Phe Ser Gin Val Asn Asn Val Leu Leu Glu

239 Arg Thr He Glu Thr Leu Leu Glu Cys Lys Asn Glu Tyr Val Lys Gly Glu Asn Gly Lys

259 Tyr Leu Ala Lys Gly His His Cys Val Glu Glu Asp Asn Leu Glu Arg Tφ Leu Gin Gly Thr Asn Glu Arg Arg Ser Glu Glu Asn He Lys Tyr Lys Tyr Gly Val Thr Glu Leu Lys He Lys Tyr Ala Gin Met Asn Gly Lys Arg Ser Ser Arg He Leu Lys Glu Ser He Tyr Gly Ala His Asn Phe Gly Gly Asn Ser Tyr Met Glu Gly Lys Asp Gly Gly Asp Lys Thr Gly Glu Glu Lys Asp Gly Glu His Lys Thr Asp Ser Lys Thr Asp Asn Gly Lys Gly Ala Asn Asn Leu Val Met Leu Asp Tyr Glu Thr Ser Ser Asn Gly Gin Pro Ala Gly Thr Leu Asp Asn Val Leu Glu Phe Val Thr Gly His Glu Gly Asn Ser Arg Lys Asn Ser Ser Asn Gly Gly Asn Pro Tyr Asp He Asp His Lys Lys Thr He Ser Ser Ala He He Asn His Ala Phe Leu Gin Asn Thr Val Met Lys Asn Cys Asn Tyr Lys Arg Lys Arg Arg Glu Arg Asp Trp Asp Cys Asn Thr Lys Lys Asp Val Cys He Pro Asp Arg Arg Tyr Gin Leu Cys Met Lys Glu Leu Thr Asn Leu Val Asn Asn Thr Asp Thr Asn Phe His Arg Asp lie Thr Phe Arg Lys Leu Tyr Leu Lys Arg Lys Leu He Tyr Asp Ala Ala Val Glu Gly Asp Leu Leu Leu Lys Leu Asn Asn Tyr Arg Tyr Asn Lys Asp Phe Cys Lys Asp He Arg Trp Ser Leu Gly Asp Phe Gly Asp He He Met Gly Thr Asp Met Glu He Gly Tyr Ser Lys Val Val Glu Asn Asn Leu Arg Ser He Phe Gly Thr Asp Glu Lys Ala Gin Gin Arg Arg Lys Gin Trp Trp Asn Glu Ser Lys Ala Gin He Trp Thr Ala Met Met Tyr Ser Val Lys Lys Arg Leu Lys Gly Asn Phe He Trp He Cys Lys Leu Asn Val Ala Val Asn lie Glu Pro Gin He Tyr Arg Tφ He Arg Glu Tφ Gly Arg Asp Tyr Val Ser Glu Leu Pro Thr Glu Val Gin Lys Leu Lys Glu Lys Cys Asp Gly Lys He Asn Tyr Thr Asp Lys Lys Val Cys Lys Val Pro Pro Cys Gin Asn Ala Cys Lys Ser Tyr Asp Gin Trp He Thr Arg Lys Lys Asn Gin Trp Asp Val Leu Ser Asn Lys Phe He Ser Val Lys Asn Ala Glu Lys Val Gin Thr Ala Gly He Val Thr Pro Tyr Asp He Leu Lys Gin Glu Leu Asp Glu Phe Asn Glu Val Ala Phe Glu Asn Glu He Asn Lys Arg Asp Gly Ala Tyr He Glu Leu Cys Val Cys Ser Val Glu Glu Ala Lys Lys Asn Thr Gin Glu Val Val Thr Asn Val Asp Asn Ala Ala Lys Ser Gin Ala Thr Asn Ser Asn Pro He Ser Gin Pro Val Asp Ser Ser Lys Ala Glu Lys Val Pro Gly Asp Ser Thr His Gly Asn Val Asn Ser Gly Gin Asp Ser Ser Thr Thr Gly Lys Ala Val Thr Gly Asp Gly Gin Asn Gly Asn Gin Thr Pro Ala Glu Ser Asp Val Gin Arg Ser Asp lie Ala Glu Ser Val Ser Ala Lys Asn Val Asp Pro Gin Lys Ser Val Ser Lys Arg Ser Asp Asp Thr Ala Ser Val Thr Gly He Ala Glu Ala Gly Lys Glu Asn Leu Gly Ala Ser Asn Ser Arg Pro Ser Glu Ser Thr Val Glu Ala Asn Ser Pro Gly Asp Asp Thr Val Asn Ser Ala Ser He 867 Pro Val Val Ser Gly Glu Asn Pro Leu Val Thr Pro Tyr Asn Gly Leu Arg His Ser Lys

887 Asp Asn Ser Asp Ser Asp Gly Pro Ala Glu Ser Met Ala Asn Pro Asp Ser Asn Ser Lys

907 Gly Glu Thr Gly Lys Gly Gin Asp Asn Asp Met Ala Lys Ala Thr Lys Asp Ser Ser Asn

927 Ser Ser Asp Gly Thr Ser Ser Ala Thr Gly Asp Thr Thr Asp Ala Val Asp Arg Glu He

947 Asn Lys Gly Val Pro Glu Asp Arg Asp Lys Thr Val Gly Ser Lys Asp Gly Gly Gly Glu

967 Asp Asn Ser Ala Asn Lys Asp Ala Ala Thr Val Val Gly Glu Asp Arg He Arg Glu Asn

987 Ser Ala Gly Gly Ser Thr Asn Asp Arg Ser Lys Asn Asp Thr Glu Lys Asn Gly Ala Ser

1007 Thr Pro Asp Ser Lys Gin Ser Glu Asp Ala Thr Ala Leu Ser Lys Thr Glu Ser Leu Glu

1027 Ser Thr Glu Ser Gly Asp Arg Thr Thr Asn Asp Thr Thr Asn Ser Leu Glu Asn Lys Asn

1047 Gly Gly Lys Glu Lys Asp Leu Gin Lys His Asp Phe Lys Ser Asn Asp Thr Pro Asn Glu

1067 Glu Pro Asn Ser Asp Gin Thr Thr Asp Ala Glu Gly His Asp Arg Asp Ser He Lys Asn

1087 Asp Lys Ala Glu Arg Arg Lys His Met Asn Lys Asp Thr Phe Thr Lys Asn Thr Asn Ser

1107 His His Leu Asn Ser Asn Asn Asn Leu Ser Asn Gly Lys Leu Asp He Lys Glu Tyr Lys

1127 Tyr Arg Asp Val Lys Ala Thr Arg Glu Asp He He Leu Met Ser Ser Val Arg Lys Cys Asn

1148 Asn Asn He Ser Leu Glu Tyr Cys Asn Ser Val Glu Asp Lys He Ser Ser Asn Thr Cys

1168 Ser Arg Glu Lys Ser Lys Asn Leu Cys Cys Ser He Ser Asp Phe Cys Leu Asn Tyr Phe

1188 Asp Val Tyr Ser Tyr Glu Tyr Leu Ser Cys Met Lys Lys Glu Phe Glu Asp Pro Ser Tyr

1208 Lys Cys Phe Thr Lys Gly Gly Phe Lys He Asp Lys Thr Tyr Phe Ala Ala Ala Gly Ala

1228 Leu Leu He Leu Leu Leu Leu He Ala Ser Arg Lys Met He Lys Asn Asp lle-COOH

A5 Examples of TNF-receptor malaria peptide fusion peptide. In the following example the TNF receptor sequence is in accordance with H Loetscher et al Cell, Vol. 61, 351-359, April 20; 1990, p353, Fig.2A, the malaria parasite components as referenced herein before,

A5 NH.-TNF-R - GBP 130-COOH

An example of a polymer of an amino acid repeat sequence.

NH₂ - He Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg 20 Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Asn Asn Ser He Cys Cys Thr 40 Lys Cys His Lys Gly Thr Tyr Leu Tyr Asn Asp Cys Pro Gly Pro Gly Gin Asp Thr Asp

120 Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin

179 Glu Asn Val Lys Gly Thr 3lu Asp Ser Gly Thr Asn Ala Tyr He Cys Gly Asp Lys Tyr

299 Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr 219 Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr 239 Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys 259 Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn 279 He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys

300 Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys 320 Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn 340 Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr [ Leu Thr Ser Ala Asp Pro Glu Gly 360 Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu lie Phe Tyr Lys 381 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu 419 Asp \ Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu nnn Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu nnn Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

A6 NH.-TNF-R - GBPH-COOH (glycophorin binding peptide homologue) An example of a polymer of an amino acid repeat sequence. NH₂ - He Tyr Pro Ser Gly Val He Gly Leu Val Pro His Leu Gly Asp Arg Glu Lys Arg

20 Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Asn Asn Ser lie Cys Cys Thr

80 Ser Cys Ser Lys Cys Arg Lys Glu Met Gly Gin Val Glu lie Ser Ser Cys Thr Val Asp 100 Arg Asp Thr Val Cys Gly Cys Arg Lys Asn Gin Tyr Arg His Tyr Trp Ser Glu Asn Leu

120 Phe Gin Cys Phe Asn Cys Ser Leu Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin 139 Glu Lys Gin Asn Thr Val Cys Thr Cys His Ala Gly Phe Phe Leu Arg Glu Asn Glu Cys 159 Val Ser Cys Ser Asn Cys Lys Lys Ser Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He 179 Glu Asn Val Lys Gly Thr Glu Asp Ser Gly Thr Ser Gin Tyr Lys Gin Ala Ala Asp Tyr 199 Ser Phe Arg Glu Ser Arg Val Leu Ala Glu Gly Lys Ser Thr Ser Lys Lys Asn Ala Lys 219 Thr Ala Leu Arg Lys Thr Lys Gin Thr Thr Leu Iτhr Ser Ala Asp Pro Glu Gly Gin He 239 Met Lys Ala Trp Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Asn Val Leu Tyr Gin He 259 Leu Asn Asn Thr Asp Pro Asn Asp Glu Leu Glu \ Thr Ser Ala Asp Pro Glu Gly Gin nnn He Met Lys Ala Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Val Asn Val Leu Tyr Gin He nnn Leu Asn Asn Thr Asp Pro Asn Asp Glu Ser Ser-COOH

Where n = a real number.

B1 NH. TNFR - GBP130-COOH

NH₂- Gly Leu Val Pro His Leu Gly Asp Arg Glu Leu Arg Asp Ser Val Cys Pro Gin Gly

20 Lys Tyr He His Pro Gin Asn Asn Ser He Cys Cys Thr Lys Cys His Lys Gly Thr Tyr Leu

41 Tyr Asn Asp Cys Pro Gly Pro Gly Gin Asp Thr Asp Cys Arg Glu Cys Glu Ser Gly Ser

61 Phe Thr Ala Ser Glu Asn His Leu Arg His Cys Leu Ser Cys Ser Lys Cys Arg Lys Glu

81 Met Gly Gin Val Glu He Ser Ser Cys Thr Val Asp Arg Asp Thr Val Cys Gly Cys Arg

101 Lys Asn Gin Tyr Arg His Tyr Trp Ser Glu Asn Leu Phe Gin Cys Phe Asn Cys Ser Leu

121 Cys Leu Asn Gly Thr Val His Leu Ser Cys Gin Glu Lys Gin Asn Thr Val Cys Thr Cys 141 His Ala Gly Phe Phe Leu Arg Glu Asn Glu Cys Val Ser Cys Ser Asn Cys Lys Lys Ser 161 Leu Glu Cys Thr Lys Leu Cys Leu Pro Gin He Glu Asn Asn Ala Tyr He Cys Gly Asp 181 Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu 201 Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr 21 Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu 41 Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin 61 He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys 82 Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser 302 Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser

322 Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro

342 Glu Gly Gin lie Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

363 Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

383 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp

403 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

423 Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

443 Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Vaf Phe His

464 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys

484 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

504 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

524 Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly

544 Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys

564 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

584 Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr

604 Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val

624 Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He

644 Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu

665 Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu

685 Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys

706 His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg

726 Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg

746 Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn

767 Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser

787 Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His

807 Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg

827 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

847 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr

868 Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH NH. - TBPI - GBP130 - COOH

NH₂ - Asp Ser Val Cys Pro Gin Gly Lys Tyr He His Pro Gin Gly Gin Val Glu He Ser Ser Cys Thr Val Asp Arg Asp Thr Val He Glu Asn Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His 566 Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg

586 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

606 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr

627 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

647 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu

667 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn

687 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr

707 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp

728 Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

D1 NH. - TBPII - GBP130 - COOH

NH₂ - Ala Gin Val Ala Phe Thr Pro Tyr Ala Pro Glu Pro Gly Ser Thr Cys Arg Leu Arg

20 Glu Tyr Tyr Asp Gin Thr Ala Gin Met Cys Cys Ser Thr Ser Asp Thr Val Cys Asp Ser

40 Cys Glu Asp Ser Thr Tyr Thr Gin Leu Trp Asn He Cys Thr Cys Arg Pro Gly Trp Tyr

60 Cys Ala Leu Ser Cys Arg Pro Gly Phe Gly Val Ala Arg Pro Gly Thr Glu Thr Ser Asp

80 Val Val Cys Lys Pro Cys Ala Pro Gly Thr Phe Ser Asn Ala Tyr lie Cys Gly Asp Lys

100 Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp

120 Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg

140 Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin

160 Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He

180 Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu 01 Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys 21 Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn 41 Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu 61 Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr 82 Lys lie Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys 02 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro 22 Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp 42 Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly 362 Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys

403 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

423 Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu

443 Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu

463 Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin

483 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He

504 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu

524 Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys

545 His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg

565 Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg

585 Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys lie Leu Thr Asn

606 Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser

626 Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His

646 Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg

666 Asn Ala Asp Asή Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

686 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr

707 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

727 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu

747 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn

767 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr

787 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp

808 Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

D2 NH. - TNFR - GBP 130 - COOH

60 Cys Ala Leu Ser Cys Arg Pro Gly Phe Gly Val Ala Arg Pro Gly Thr Glu Thr Ser Thr

80 Val Val Cys Lys Pro Cys Ala Pro Gly Thr Phe Ser Asn Ala Tyr He Cys Gly Asp Lys 100 Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp

180 Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu

201 Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys

221 Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn

241 Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu

261 Gly Gin He Met Arg Glu Thr Ala,Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

282 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys

302 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro

322 Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp

342 Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly

362 Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys

383 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

403 Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu

423 Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu

443 Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin

463 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He

484 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu

504 Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys

525 His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg

545 Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg

565 Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn

586 Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser

606 Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His

626 Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg

646 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

666 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr 687 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

707 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu

727 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn

747 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

767 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp

788 Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

E1 NH. - ylFN-R - GBP 130 - COOH

,NH₂ Ser Arg Ala Glu Met Gly Thr Ala Asp Leu Gly Pro Ser Ser Val Pro Thr Pro Thr

20 Asn Val Thr He Glu Ser Tyr Asn Met Asn Pro He Val Tyr Trp Glu Tyr Gin He Met

40 . Pro Gin Val Pro Val Phe Thr Val Glu Val Lys Asn Tyr Gly Val Lys Asn Ser Glu Trp

60 He Asp Ala Cys He Asn He Ser His His Tyr Cys Asn He Ser Asp His Val Gly Asp Pro

81 Ser Asn Ser Leu Trp Val Arg Val Lys Ala Arg Val Gly Gin Lys Glu Ser Ala Tyr Ala Lys

102 Ser Glu Glu Phe Ala Val Cys Arg Asp Gly Lys He Gly Pro Pro Lys Leu Asp lie Arg

122 Lys Glu Glu Lys Gin He Met He Asp He Phe His Pro Ser Val Phe Val Asn Gly Asp Glu

143 Gin Glu Val Asp Tyr Asp Pro Glu Thr Thr Cys Tyr He Arg Val Tyr Asn Val Tyr Val Arg

164 Met Asn Gly Ser Glu He Gin Tyr Lys He Leu Thr Gin Lys Glu Asp Asp Cys Asp Glu

184 He Gin Cys Gin Leu Ala He Pro Val Ser Ser Leu Asn Ser Gin Tyr Cys Val Ser Ala Glu 05 Gly Val Leu His Val Trp Gly Val Thr Thr Glu Lys Ser Lys Glu Val Cys lie Thr He Phe 26 Asn Ser Ser He Lys Gly Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr 47 Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys 67 Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys 87 Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu 07 Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin 28 Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys 49 Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys 69 Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser 90 Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala 10 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro 430 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro

450 Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

471 Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn

491 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

511 Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn

531 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

551 Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His

572 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys

592 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

611 Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

631 Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin

651 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He

671 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp

691 Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg

712 Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu

732 Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met

752 Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr

773 Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr

793 Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His

814 Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg

834 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

854 Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr

875 Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

895 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

915 Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn

935 Ala Asp Asn Asn Glu Ala-COOH NH. - IL-1R type II - GBP 130 - COOH

NH₂- Met Leu Arg Leu Tyr Val Leu Val Met Gly Val Ser Ala Phe Thr Leu Gin Pro Ala Ala His Thr Gly Ala Ala Arg Ser Cys Arg Phe Arg Gly Arg His Tyr Lys Arg Glu Phe Arg Leu Glu Gly Glu Pro Val Ala Leu Arg Cys Pro Gin Val Pro Tyr Trp Leu Trp Ala Ser Val Ser Pro Arg He Asn Leu Thr Trp His Lys Asn Asp Ser Ala Arg Thr Val Pro Gly Glu Glu Glu Thr Arg Met Trp Ala Gin Asp Gly Ala Leu Trp Leu Leu Pro Ala Leu Gin Glu Asp Ser Gly Thr Tyr Val Cys Thr Thr Arg Asn Ala Ser Tyr Cys Asp Lys Met Ser He Glu He Leu Arg Val Phe Glu Asn Thr Asp Ala Phe Leu Pro Phe He Ser Tyr Pro Asp He Leu Thr Leu Ser Thr Ser Gly Val Leu Val Cys Phe Asp Leu Ser Glu Phe Thr Arg Asp Lys Thr Asp Val Lys He Asp Trp Tyr Lys Asp Ser Leu Leu Leu Asp Lys Asp Asn Glu Lys Phe Leu Ser Val Arg Gly Thr Thr His Leu Leu Val His Asp Val Ala Leu Glu Asp Arg Gly Tyr Tyr Arg Cys Val Leu Thr Phe Ala His Glu Gly Gin Gin Tyr Asn He Thr Arg Ser He Glu Leu Arg He Lys Lys Lys Lys Glu Glu Thr He Pro His He He Ser Pro Leu Lys Thr He Ser Arg Ser Leu Gly Ser Arg Leu Thr lie Pro Cys Lys Val Phe Leu Gly Thr Gly Thr Pro Leu Thr Thr Met Leu Trp Trp Thr Ala Asn Asp Thr His He Glu Ser Ala Tyr Pro Gly Gly Arg Val Thr Glu Gly Pro Arg Gin Glu Tyr Ser Glu Asn Asn Glu Asn Tyr He Glu Val Pro Leu He Phe Asp Pro Val Thr Arg Glu Asp Leu His Met Asp Phe Lys Cys Val Val His Asn Thr Leu Ser Phe Gin Thr Leu Arg Thr Thr Val Lys Glu Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly 565 Gin lie Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys

586 He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

606 Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu

626 Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu

646 Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin

666 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He

687 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp

707 Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glϋ Tyr Arg

727 Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu

747 Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg

767 Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn

788 Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser

808 Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

829 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

849 Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr

869 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp

890 Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp

910 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

931 Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

951 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser

971 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

991 Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro

1010 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

1030 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn

1050 Asn Glu Ala-COOH

G1 1 -IL1R type 1 - GBP13Q - COOH

NH₂- Met Lys Val Leu Leu Arg Leu He Cys Phe He Ala Leu Leu He Ser Ser Leu Glu

20 Ala Asp Lys Cys Lys Glu Arg Glu Glu Lys He He Leu Val Ser Ser Ala Asn Glu He Asp Val Arg Pro Cys Pro Leu Asn Pro Asn Glu His Lys Gly Thr He Thr Trp Tyr Lys Asp Asp Ser Lys Thr Pro Val Ser Thr Glu Gin Ala Ser Arg He His Gin His Lys Glu Lys Leu Trp Phe Val Pro Ala Lys Val Glu Asp Ser Gly His Tyr Tyr Cys Val Val Arg Asn Ser Ser Tyr Cys Leu Arg He Lys He Ser Ala Lys Phe Val Glu Asn Glu Pro Asn Leu Cys Tyr Asn Ala Gin Ala He Phe Lys Asp Lys Leu Pro Val Ala Gly Asp Gly Gly Leu Val Cys Phe Tyr Met Glu Phe Phe Lys Asn Glu Asn Asn Glu Leu Pro Lys Leu Trp Tyr Lys Asp Cys Lys Pro Leu Leu Leu Asp Asn He His Phe Ser Gly Val Lys Asp Arg Leu He Val Met Asn Val Arg Glu Lys His Arg Gly Asn Tyr Thr Cys His Ala Ser Tyr Thr Tyr Leu Gly Lys Gin Tyr Pro He Thr Arg Val He Glu Phe He Thr Leu Glu Glu Asn Lys Pro Thr Arg Pro His He Val Ser Pro Ala Asn Glu Thr Met Glu Val Asp Leu Gly Ser Gin He Gin Leu He Cys Asn Val Thr Gly Gin Leu Ser Asp He Ala Tyr Trp Lys Trp Asn Gly Ser Val He Asp Glu Asp Asp Pro Val Leu Gly Glu Asp Tyr Tyr Ser Val Glu Asn Pro Ala Asn Lys Arg Arg Ser Thr Leu He Thr Val Leu Asn He Ser Glu He Glu Ser Arg Phe Tyr Lys His Pro Phe Thr Cys Phe Ala Lys Asn Thr His Gly He Asp Ala Ala Tyr He Gin Leu He Tyr Pro Val Thr Asn Phe Gin Lys Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys lie Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys lie Leu Thr Asn Thr 630 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

650 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

670 Glu lie Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

690 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

710 Ala Ala Asp Pro Glu Thr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

730 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

750 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

771 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

791 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

811 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

831 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

851 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

872 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

892 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

912 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

932 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

952 Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

973 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys

993 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

1013 Glu Tyr Arg Lys His Leu Glu lie Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

1033 Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

H1 NH. - IL2-R - GBP 130 - COOH

NH₂-Glu Leu Cys Asp Asp Asp Pro Pro Glu He Pro His Ala Thr Phe Lys Ala Met Ala

20 Tyr Lys Glu Gly Thr Met Leu Asn Cys Glu Cys Lys Arg Gly Phe Arg Arg He Lys Ser

40 Gly Ser Leu Tyr Met Leu Cys Thr Gly Asn Ser Ser His Ser Ser Tφ Asp Asn Gin Cys

60 Gin Cys Thr Ser Ser Ala Thr Arg Asn Thr Thr Lys Gin Val Thr Pro Gin Pro Glu Glu

80 Gin Lys Glu Arg Lys Thr Thr Glu Met Gin Ser Pro Met Gin Pro Val Asp Gin Ala Ser

100 Leu Pro Gly His Cys Arg Glu Pro Pro Pro Trp Glu Asn Glu Ala Thr Glu Arg He Tyr His Phe Val Val Gly Gin Met Val Tyr Tyr Gin Cys Val Gin Gly Tyr Arg Ala Leu His Arg Gly Pro Ala Glu Ser Val Cys Lys Met Thr His Gly Lys Thr Arg Trp Thr Gin Pro Gin Leu He Cys Thr Gly Glu Met Glu Thr Ser Gin Phe Pro Gly Glu Glu Lys Pro Gin Ala Ser Pro Glu Gly Arg Pro Glu Ser Glu Thr Ser Cys Leu Val Thr Thr Thr Asp Phe Gin He Gin Thr Glu Met Ala Ala Thr Met Glu Thr Ser He Phe Thr Thr Glu Tyr Gin Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr 710 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys

730 Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

750 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

770 Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly

790 Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys

811 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

831 Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu

851 Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp

871 Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin

891 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He

911 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu

930 Ala-COOH

H2 NH. - IL 2-R - C.PB 130 - COOH

NH₂-Ala Glu Leu Cys Asp Asp Asp Pro Pro Glu He Pro His Ala Thr Phe Lys Ala Met

20 Ala Tyr Lys Glu Gly Thr Met Leu Asn Cys Glu Cys Lys Arg Gly Phe Arg Arg He Lys

40 Ser Gly Ser Leu Tyr Met Leu Cys Thr Gly Asn Ser Ser His Ser Ser Trp Asp Asn Gin

60 Cys Gin Cys Thr Ser Ser Ala Thr Arg Asn Thr Thr Lys Gin Val Thr Pro Gin Pro Glu

80 Glu Gin Lys Glu Arg Lys Thr Thr Lys lie Gin Ser Pro Met Gin Pro Val Asp Gin Ala

100 Ser Leu Pro Gly His Cys Arg Glu Pro Pro Pro Tφ Glu Asn Glu Ala Thr Glu Arg He

120 Tyr His Phe Val Val Gly Gin Met Val Tyr Tyr Gin Cys Val Gin Gly Tyr Arg Ala Leu His

141 Arg Gly Pro Ala Glu Ser Val Cys Lys Met Thr His Gly Lys Thr Arg Tφ Thr Gin Pro

161 Gin Leu He Cys Thr Gly Glu Met Glu Thr Ser Gin Phe Pro Gly Glu Glu Lys Pro Gin

181 Ala Ser Pro Glu Gly Arg Pro Glu Ser Glu Thr Ser Cys Leu Val Thr Thr Thr Asp Phe 01 Gin He Gin Thr Glu Met Ala Ala Thr Met Glu Thr Ser He Phe Thr Thr Glu Tyr Asn Ala 22 Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg lie Leu 43 Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin 63 Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val 83 Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu lie Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin 889 lie Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu lie Phe His Lys He

910 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu

929 Ala-COOH

H3 j^jd₂ - IL2-R - GBP 13Q - COOH

NH₂-Ala Val Asn Gly Thr Ser Gin Phe Thr Cys Phe Tyr Asn Ser Arg Ala Asn He Ser

20 Cys Val Trp Ser Gin Asp Gly Ala Leu Gin Asp Thr Ser Cys Gin Val His Ala Trp Pro

40 Asp Arg Arg Arg Trp Asn Gin Thr Cys Glu Leu Leu Pro Val Ser Gin Ala Ser Trp Ala

60 Cys Asn Leu He Leu Gly Ala Pro Asp Ser Gin Lys Leu Thr Thr Val Asp He Val Thr

80 Leu Arg Val Leu Cys Arg Glu Gly Val Arg Tφ Arg Val Met Ala He Gin Asp Phe Lys

100 Pro Phe Glu Asn Leu Arg Leu Met Ala Pro He Ser Leu Gin Val Val His Val Glu Thr

120 His Arg Cys Asn He Ser Tφ Glu He Ser Gin Ala Ser His Tyr Phe Glu Arg His Leu Glu

141 Phe Glu Ala Arg Thr Leu Ser Pro Gly His Thr Tφ Glu Glu Ala Pro Leu Leu Thr Leu

161 Lys Gin Lys Gin Glu Tφ He Cys Leu Glu Thr Leu Thr Pro Asp Thr Gin Tyr Glu Phe

181 Gin Val Arg Val Lys Pro Leu Gin Gly Glu Phe Thr Thr Trp Ser Pro Trp Ser Gin Pro 01 Leu Ala Phe Arg Thr Lys Pro Ala Ala Leu Gly Lys Asp Thr Asn Ala Tyr He Cys Gly 21 Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly 41 Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser 61 Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu 81 Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys 01 Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val lie Lys 22 Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala 42 Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg 62 Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp 82 Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He 03 Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp 23 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser 43 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro 63 Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

ld₂ - IL-3R - GBP 130 - COOH

NH₂- Thr Lys Glu Asp Pro Asn Pro Pro He Thr Asn Leu Arg Met Lys Ala Lys Ala Gin Gin Leu Thr Tφ Asp Leu Asn Arg Asn Val Thr Asp He Glu Cys Val Lys Asp Ala Asp Tyr Ser Met Pro Ala Val Asn Asn Ser Tyr Cys Gin Phe Gly Ala He Ser Leu Cys Glu Val Thr Asn Tyr Thr Val Arg Val Ala Asn Pro Pro Phe Ser Thr Tφ He Leu Phe Pro Glu Asn Ser Gly Lys Pro Tφ Ala Gly Ala Glu Asn Leu Thr Cys Tφ He His Asp Val 100 Asp Phe Leu Ser Cys Ser Trp Ala Val Gly Pro Gly Ala Pro Ala Asp Val Gin Tyr Asp

120 Leu Tyr Leu Asn Val Ala Asn Arg Arg Gin Gin Tyr Glu Cys Leu His Tyr Lys Thr Asp

140 Ala Gin Gly Thr Arg He Gly Cys Arg Phe Asp Asp He Ser Arg Leu Ser Ser Gly Ser

160 Gin Ser Ser His He Leu Val Arg Gly Arg Ser Ala Ala Phe Gly He Pro Cys Thr Asp

180 Lys Phe Val Val Phe Ser Gin He Glu He Leu Thr Pro Pro Asn Met Thr Ala Lys Cys

200 Asn Lys Thr His Ser Phe Met His Trp Lys Met Arg Ser His Phe Asn Arg Lys Phe Arg

220 Tyr Glu Leu Gin He Gin Lys Arg Met Gin Pro Val He Thr Glu Gin Val Arg Asp Arg Thr

241 Ser Phe Gin Leu Leu Asn Pro Gly Thr Tyr Thr Val Gin He Arg Ala Arg Glu Arg Val

261 Tyr Glu Phe Leu Ser Ala Trp Ser Thr Pro Gin Arg Phe Glu Cys Asp Gin Glu Glu Gly

281 Ala Asn Thr Arg Ala Trp Arg Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp

302 Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu

322 Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr

342 Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser

362 Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn

383 Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly

404 Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser

424 Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala

445 Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala

465 Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

486 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro

506 Glu Gly Gin lie Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

527 Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn

547 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

567 Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn

587 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

607 Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His

628 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys

648 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

668 Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

NH. - IL-5R - GBP 130 - COOH

NH₂-Met Lys Val Leu Gin Glu Pro Thr Cys Val Ser Asp Thr Met Ser He Ser Thr Cys Glu Trp Lys Met Asn Gly Pro Thr Asn Cys Ser Thr Glu Leu Arg Leu Leu Tyr Gin Leu Val Phe Leu Leu Ser Glu Ala His Thr Cys He Pro Glu Asn Asn Gly Gly Ala Gly Cys Val Cys His Leu Leu Met Asp Asp Val Val Ser Ala Asp Asn Tyr Thr Leu Asp Leu Tφ Ala Gly Gin Gin Leu Leu Tφ Lys Gly Ser Phe Lys Pro Ser Glu His Val Lys Pro Arg Ala Pro Gly Asn Leu Thr Val His Thr Asn Val Ser Asp Thr Leu Leu Leu Thr Trp Ser Asn Pro Tyr Pro Pro Asp Asn Tyr Leu Tyr Asn His Leu Thr Tyr Ala Val Asn He Trp Ser Glu Asn Asp Pro Ala Asp Phe Arg He Tyr Asn Val Thr Tyr Leu Glu Pro Ser Leu Arg He Ala Ala Ser Thr Leu Lys Ser Gly He Ser Tyr Arg Ala Arg Val Arg Ala Trp Ala Gin Cys Tyr Asn Thr Thr Trp Ser Glu Trp Ser Pro Ser Thr Lys Trp His Asn Ser Tyr Arg Glu Pro Phe Glu Gin His Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val 221 Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys

241 Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin

261 Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp

281 Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin lie Asn He Gly Asp Thr Glu

302 Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu

322 Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys

342 Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg

363 Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

383 Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr

404 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

420 Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu

444 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn

464 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

484 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

504 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

524 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

544 Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

564 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

584 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

604 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

624 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

645 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

665 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

685 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

705 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

725 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

746 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

766 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

786 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu lie Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

NH.-IL-βR - GBP 130 - COOH

NH₂ - Asp Leu Leu Pro Asp Glu Lys He Ser Leu Leu Pro Pro Val Asn Phe Thr He Lys Val Thr Gly Leu Ala Gin Val Leu Leu Gin Trp Lys Pro Asn Pro Asp Gin Glu Gin Arg Asn Val Asn Leu Glu Tyr Gin Val Lys He Asn Ala Pro Lys Glu Asp Asp Tyr Glu Thr Arg He Thr Glu Ser Lys Cys Val Thr He Leu His Lys Gly Phe Ser Ala Ser Val Arg Thr He Leu Gin Asn Asp His Ser Leu Leu Ala Ser Ser Trp Ala Ser Ala Glu Leu His Ala Pro Pro Gly Ser Pro Gly Thr Ser He Val Asn Leu Thr Cys Thr Thr Asn Thr Thr Glu Asp Asn Tyr Ser Arg Leu Arg Ser Tyr Gin Val Ser Leu His Cys Thr Trp Leu Val Gly Thr Asp Ala Pro Glu Asp Thr Gin Tyr Phe Leu Tyr Tyr Arg Tyr Gly Ser Trp Thr Glu Glu Cys Gin Glu Tyr Ser Lys Asp Thr Leu Gly Arg Asn He Ala Cys Trp Phe Pro Arg Thr Phe He Leu Ser Lys Gly Arg Asp Trp Leu Ser Val Leu Val Asn Gly Ser Ser Lys His Ser Ala He Arg Pro Phe Asp Gin Leu Phe Ala Leu His Ala He Asp Gin He Asn Pro Pro Leu Asn Val Thr Ala Glu lie Glu Gly Thr Arg Leu Ser He Gin Trp Glu Lys Pro Val Ser Ala Phe Pro He His Cys Phe Asp Tyr Glu Val Lys He His Asn Thr Arg Asn Gly Tyr Leu Gin He Glu Lys Leu Met Thr Asn Ala Phe lie Ser He He Asp Asp Leu Ser Lys Tyr Asp Val Gin Val Arg Ala Ala Val Ser Ser Met Cys Arg Glu Ala Gly Leu Trp Ser Glu Tφ Ser Gin Pro He Tyr Val Gly Phe Ser Arg Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys 428 Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys

448 Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu

468 Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He

489 Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu

510 Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu

530 Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys

551 His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg

571 Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg

591 Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr

611 Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr

631 Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His

652 Leu Glu lie Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg

672 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

692 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

713 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

733 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

754 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

774 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

794 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

8 4 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

834 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

855 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

875 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

896 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

916 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

936 Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

957 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys

977 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

997 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp 1017 Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

L1 NH. - IL-β R type 1 - GBP 130 - COOH

NH₂ - Leu Ala Pro Arg Arg Cys Pro Ala Gin Glu Val Ala Arg Gly Val Leu Thr Ser Leu 0 Pro Gly Asp Ser Val Thr Leu Thr Cys Pro Gly Val Glu Pro Glu Asp Asn Ala Thr Val 0 His Trp Val Leu Arg Lys Pro Ala Ala Gly Ser His Pro Ser Arn Trp Ala Gly Met Gly Arg

61 Arg Leu Leu Leu Arg Ser Val Gin Leu His Asp Ser Gly Asn Tyr Ser Cys Tyr Ala Gly

81 Arg Pro Ala Gly Thr Val His Leu Leu Val Asp Val Pro Pro Glu Glu Pro Gin Leu Ser

101 Cys Phe Arg Lys Ser Pro Leu Ser Asn Val Val Cys Glu Trp Gly Pro Arg Ser Thr Pro

121 Ser Leu Thr Thr Lys Ala Val Leu Leu Val Arg Lys Phe Gin Asn Ser Pro Ala Glu Asp

141 Phe Gin Glu Ser Gin Lys Phe Ser Cys Gin Leu Ala Val Pro Glu Gly Asp Ser Ser Phe

161 Tyr He Val Ser Met Cys Val Ala Ser Ser Val Gly Ser Lys Phe Ser Lys Thr Gin Thr

181 Phe Gin Gly Cys Gly He Leu Gin Pro Asp Pro Pro Ala Asn He Thr Val Thr Ala Val Ala 02 Arg Asn Pro Arg Trp Leu Ser Val Thr Tφ Gin Asp Pro His Ser Trp Asn Ser Ser Phe 22 Tyr Arg Leu Arg Phe Glu Leu Arg Tyr Arg Ala Glu Arg Ser Lys Thr Phe Thr Thr Trp 42 Met Val Lys Asp Leu Gin His His Cys Val He His Asp Ala Trp Ser Gly Leu Arg His Val 63 Val Gin Leu Arg Ala Gin Glu Glu Phe Gly Gin Gly Glu Tφ Ser Glu Trp Ser Pro Glu 83 Ala Met Gly Thr Pro Trp Thr Glu Ser Arg Ser Pro Pro Ala Glu Asn Glu Val Ser Thr 03 Pro Met Gin Ala Leu Thr Thr Asn Lys Asp Asp Asp Asn He Leu Phe Arg Asp Ser Ala 23 Asn Ala Thr Ser Leu Pro Val Gin Asp Asn Ala Tyr lie Cys Gly Asp Lys Tyr Glu Lys 43 Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala 63 Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala 83 Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu 04 Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp 25 Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys 45 Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu 65 Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val 85 Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met 06 Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr 527 Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr

547 Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His

568 Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg

588 Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu

608 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

629 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

649 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

669 Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

689 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

709 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys lie Leu Thr Asn Thr

729 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

749 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

770 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

790 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

810 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

830 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

850 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

871 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

891 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

911 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

931 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

951 Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

972 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys

992 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

1011 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

1031 Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH NH. - IL-8 R type 1 - GBP 130 - COOH

NH₂-Met Ser Asn He Thr Asp Pro Gin Met Trp Asp Phe Asp Asp Leu Asn Phe Thr Gly Met Pro Pro Ala Asp Glu Asp Tyr Ser Pro Cys Met Leu Glu Thr Glu Thr Leu Asn Lys Tyr Val Val He He Ala Tyr Ala Leu Val Phe Leu Leu Ser Leu Leu Gly Asn Ser Leu Val Met Leu Val He Leu Tyr Ser Arg Val Gly Arg Ser Val Thr Asp Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu Phe Ala Leu Thr Leu Pro He Trp Ala Ala Ser Lys Val 1 Asn Gly Trp He Phe Gly Thr Phe Leu Cys Lys Val Val Ser Leu Leu Lys Glu Val Asn 1 Phe Tyr Ser Gly He Leu Leu Leu Ala Cys He Ser Val Asp Arg Tyr Leu Ala He Val His Ala Thr Arg Thr Leu Thr Gin Lys Arg His Leu Val Lys Phe Val Cys Leu Gly Cys Tφ Gly Leu Ser Met Asn Leu Ser Leu Pro Phe Phe Leu Phe Arg Gin Ala Tyr His Pro Asn Asn Ser Ser Pro Val Cys Tyr Glu Val Leu Gly Asn Asp Thr Ala Lys Trp Arg Met Val Leu Arg He Leu Pro His Thr Phe Gly Phe He Val Pro Leu Phe Val Met Leu Phe Cys Tyr Gly Phe Thr Leu Arg Thr Leu Phe Lys Ala His Met Gly Gin Lys His Arg Ala Met Arg Val He Phe Ala Val Val Leu He Phe Leu Leu Cys Trp Leu Pro Tyr Asn Leu Val Leu Leu Ala Asp Thr Leu Met Arg Thr Gin Val He Gin Glu Thr Cys Glu Arg Arg Asn Asn He Gly Arg Ala Leu Asp Ala Thr Glu lie Leu Gly Phe Leu His Ser Cys Leu Asn Pro He He Tyr Ala Phe lie Gly Gin Asn Phe Arg His Gly Phe Leu Lys He Leu Ala Met His Gly Leu Val Ser Lys Glu Phe Leu Ala Arg His Arg Val Thr Ser Tyr Thr Ser Ser Ser Val Asn Val Ser Ser Asn Leu Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala 565 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu

585 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn

605 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

625 Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

645 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

665 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

685 Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

705 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

725 Ala Ala Asp Pro Glu Thr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

745 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

765 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

786 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

806 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

826 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

846 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

866 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

887 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

907 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

927 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

947 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

967 Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

988 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys

1008 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

1028 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

1049 Glu Val Giu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

M2 NH. - IL-8R type 2 - GBP 130 - COOH

NH₂- Met Glu Ser Asp Ser Phe Glu Asp Phe Tφ Lys Gly Glu Asp Leu Ser Asn Tyr Ser

20 Tyr Ser Ser Thr Leu Pro Pro Phe Leu Leu Asp Ala Ala Pro Cys Glu Pro Glu Ser Leu Glu He Asn Lys Tyr Phe Val Val He He Tyr Ala Leu Val Phe Leu Leu Ser Leu Leu Gly Asn Ser Leu Val Met Leu Val He Leu Tyr Ser Arg Val Gly Arg Ser Val Thr Asp Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu Phe Ala Leu Thr Leu Pro He Trp Ala Ala Ser Lys Val Asn Gly Trp He Phe Gly Thr Phe Leu Cys Lys Val Val Ser Leu Leu Lys Glu Val Asn Phe Tyr Ser Gly He Leu Leu Leu Ala Cys He Ser Val Asp Arg Tyr Leu Ala He Val His Ala Thr Arg Thr Leu Thr Gin Lys Arg Tyr Leu Val Lys Phe He Cys Leu Ser He Trp Gly Leu Ser Leu Leu Leu Ala Leu Pro Val Leu Leu Phe Arg Arg Thr ValsTyr Ser Ser Asn Val Ser Pro Ala Cys Tyr Glu Asp Met Gly Asn Asn Thr Ala Asn Trp Arg Met Leu Leu Arg He Leu Pro Gin Ser Phe Gly Phe He Val Pro Leu Leu He Met Leu Phe Cys Tyr Gly Phe Thr Leu Arg Thr Leu Phe Lys Ala His Met Gly Gin Lys His Arg Ala Met Arg Val He Phe Ala Val Val Leu He Phe Leu Leu Cys Trp Leu Pro Tyr Asn Leu Val Leu Leu Ala Asp Thr Leu Met Arg Thr Gin Val He Gin Glu Thr Cys Glu Arg Arg Asn His He Asp Arg Ala Leu Asp Ala Thr Glu He Leu Gly He Leu His Ser Cys Leu Asn Pro Leu He Tyr Ala Phe He Gly Gin Lys Phe Arg His Gly Leu Leu Lys He Leu Ala He His Gly Leu He Ser Lys Asp Ser Leu Pro Lys Asp Ser Arg Pro Ser Phe Val Gly Ser Ser Ser Gly His Thr Ser Thr Thr Leu Asn Ala Tyr He Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Gin Lys Thr Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala Asp Pro Glu Gly He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu 630 Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

650 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala

670 Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

690 Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

710 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

730 Ala Ala Asp Pro Glu Thr Arg Lys His Leu Glu Val Phe His Lys He Leu Thr Asn Thr

750 Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp

770 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He

791 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

811 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin lie Met Arg Glu Tyr Ala Ala

831 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro

851 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu Leu Thr Ser Ser Asp Pro

871 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe

892 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

912 Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp

932 Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn

952 Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu

972 Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr

993 Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys

1013 Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

1033 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

1053 Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala-COOH

N1 NH. - LIF-R - GBP 130 - COOH

NH₂-Met Arg Thr Ala Ser Asn Phe Gin Tφ Leu Leu Ser Thr Phe lie Leu Leu Tyr Leu

20 Met Asn Gin Val Asn Ser Gin Lys Lys Gly Ala Pro His Asp Leu Lys Cys Val Thr Asn 0 Asn Leu Gin Val Tφ Asn Cys Ser Tφ Lys Ala Pro Ser Gly Thr Gly Arg Gly Thr Asp

60 Tyr Glu Val Cys He Glu Asn Arg Ser Arg Ser Cys Tyr Gin Leu Glu Lys Thr Ser He Lys

81 He Pro Ala Leu Ser His Gly Asp Tyr Glu He Thr He Asn Ser Leu His Asp Phe Gly Ser 102 Ser Thr Ser Lys Phe Thr Leu Asn Glu Gin Asn Val Ser Leu He Pro Asp Thr Pro Glu

122 He Leu Asn Leu Ser Ala Asp Phe Ser Thr Ser Thr Leu Tyr Leu Lys Tφ Asn Asp Arg

142 Gly Ser Val Phe Pro His Arg Ser Asn Val He Trp Glu He Lys Val Leu Arg Lys Glu Ser

163 Met Glu Leu Val Lys Leu Val Thr His Asn Thr Thr Leu Asn Gly Lys Asp Thr Leu His

183 His Trp Ser Trp Ala Ser Asp Met Pro Leu Glu Cys Ala He His Phe Val Glu He Arg Cys

204 Tyr He Asp Asn Leu His Phe Ser Gly Leu Glu Glu Trp Ser Asp Trp Ser Pro Val Lys

224 Asn Asn Ser Trp He Pro Asp Ser Gin Thr Lys Val Phe Pro Gin Asp Lys Val He Leu

244 Val Gly Ser Asp He Thr Phe Cys Cys Val Ser Gin Glu Lys Val Leu Ser Ala Leu He Gly

265 His Thr Asn Cys Pro Leu He His Leu Asp Gly Glu Asn Val Ala He Lys He Arg Asn He

286 Ser Val Ser Ala Ser Ser Gly Thr Asn Val Val Phe Thr Thr Glu Asp Asn He Phe Gly

306 Thr Val He Phe Ala Gly Tyr Pro Pro Asp Thr Pro Gin Gin Leu Asn Cys Glu Thr His

326 Asp Leu Lys Glu He He Cys Ser Trp Asn Pro Gly Arg Val Thr Ala Leu Val Gly Pro Arg

347 Ala Thr Ser Tyr Thr Leu Val Glu Ser Phe Ser Gly Lys Tyr Val Arg Leu Lys Arg Ala

367 Glu Ala Pro Thr Asn Glu Ser Tyr Gin Leu Leu Phe Gin Met Leu Pro Asn Gin Glu He

387 Tyr Asn Phe Thr Leu Asn Ala His Asn Pro Leu Gly Arg Ser Gin Ser Thr He Leu Val

407 Asn He Thr Glu Lys Val Tyr Pro His Thr Pro Thr Ser Phe Lys Val Lys Asp He Asn Ser

428 Thr Ala Val Lys Leu Ser Tφ His Leu Pro Gly Asn Phe Ala Lys He Asn Phe Leu Cys

448 Glu He Glu He Lys Lys Ser Asn Ser Val Gin Glu Gin Arg Asn Val Thr He Gin Gly Val

469 Glu Asn Ser Ser Tyr Leu Val Ala Leu Asp Lys Leu Asn Pro Tyr Thr Leu Tyr Thr Phe

489 Arg He Arg Cys Ser Thr Glu Thr Phe Tφ Lys Tφ Ser Lys Tφ Ser Asn Lys Lys Gin

509 His Leu Thr Thr Glu Ala Ser Pro Ser Lys Gly Pro Asp Thr Trp Arg Glu Trp Ser Ser

529 Asp Gly Lys Asn Leu He He Tyr Tφ Lys Pro Leu Pro He Asn Glu Ala Asn Gly Lys He

550 Leu Ser Tyr Asn Val Ser Cys Ser Ser Asp Glu Glu Thr Gin Ser Leu Ser Glu He Pro

570 Asp Pro Gin His Lys Ala Glu He Arg Leu Asp Lys Asn Asp Tyr He He Ser Val Val Ala

591 Lys Asn Ser Val Gly Ser Ser Pro Pro Ser Lys He Ala Ser Met Glu He Pro Asn Asp

611 Asp Leu Lys He Glu Gin Val Val Gly Met Gly Lys Gly He Leu Leu Thr Trp His Tyr Asp

632 Pro Asn Met Thr Cys Asp Tyr Val lie Lys Tφ Cys Asn Ser Ser Arg Ser Glu Pro Cys

653 Leu Met Asp Tφ Arg Lys Val Pro Ser Asn Ser Thr Glu Thr Val He Glu Ser Asp Glu

672 Phe Arg Pro Gly He Arg Tyr Asn Phe Phe Leu Tyr Gly Cys Arg Asn Gin Gly Tyr Gin 692 Leu Leu Arg Ser Met He Gly Tyr lie Glu Glu Leu Ala Pro He Val Ala Pro Asn Phe Thr

713 Val Glu Asp Thr Ser Ala Asp Ser He Leu Val Lys Trp Glu Asp He Pro Val Glu Glu Leu

734 Arg Gly Phe Leu Arg Gly Tyr Leu Phe Tyr Phe Gly Lys Gly Glu Arg Asp Thr Ser Lys

754 Met Arg Val Leu Glu Ser Gly Arg Ser Asp He Lys Val Lys Asn He Thr Asp He Ser Gin

775 Lys Thr Leu Arg He Ala Asp Leu Gin Gly Lys Thr Ser Tyr His Leu Val Leu Arg Ala Tyr

796 Thr Asp Gly Gly Val Gly Pro Glu Lys Ser Met Tyr Val Val Thr Lys Asn Ala Tyr He Cys

816 Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe Arg Glu Ser Arg He Leu Ala Glu

836 Gly Glu Asp Thr Cys Ala Arg Lys Glu Lys Thr Thr Leu Arg Lys Ser Lys Glή Lys Thr

856 Ser Thr Arg Thr Val Ala Thr Gin Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr

876 Glu Glu Gin Lys Val Glu Ser Asp Ser Glu Lys Gin Lys Arg Thr Lys Lys Val Val Lys

896 Lys Gin He Asn He Gly Asp Thr Glu Asn Gin Lys Glu Gly Lys Asn Val Lys Lys Val He

917 Lys Lys Glu Lys Lys Lys Glu Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu

937 Ala Ser Lys Lys Lys Glu Pro Lys Ala Ser Lys Val Ser Gin Lys Pro Ser Thr Ser Thr

957 Arg Ser Asn Asn Glu Val Lys He Arg Ala Ala Ser Asn Gin Glu Thr Leu Thr Ser Ala

977 Asp Pro Glu Gly Gin He Met Arg Glu Thr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu

997 Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn

1017 Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr

1037 Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp

1058 Pro Asn Asp Asp Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp

1078 Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val

1099 Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp

1119 Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala

1139 Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro

1159 Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro

1179 Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe

1200 His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn

1220 Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro

1240 Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp

1260 Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly 1280 Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys

1301 He Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu

1321 Glu Leu Thr Ser Ser Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ala Asp Pro Glu

1341 Tyr Arg Lys His Leu Glu He Phe His Lys He Leu Thr Asn Thr Asp Pro Asn Asp Glu

1361 Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin

1381 He Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe Tyr Lys He

1402 Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp

1422 Leu Thr Ser Ala Asp Pro Glu Gly Gin He Met Arg Glu Tyr Ala Ser Asp Pro Glu Tyr

1442 Arg Lys His Leu Glu He Phe Tyr Lys He Leu Thr Asn Thr Asp Pro Asn Asp Asp Val

1462 Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gin He

1482 Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu He Phe His Lys He Leu

1503 Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Gin Asn Ala Asp Asn Asn Glu Ala- COOH

Claims

CLAI S

What is claimed is;

1) The hybrid peptides formed by the fusion of two or more components, one component being derived from all or part of a malaria parasite peptide capable of binding to a red blood cell and the other component being a cytokine receptor or receptor capable of binding to an inflammatory mediator or part thereof or substitutional or deletional variation there of.

2) The hybrid peptide according to claim 1 where all or part of the 55kd TNF-R Tumour Necrosis fador receptor or the 75kd TNF-R is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the TNF-R molecule is joined to the C terminal of the GBP 130 molecule.

3) The hybrid peptide according to daim 1 where all or part of the TBPI Tumour Necrosis fador binding peptide type 1 or TBPII is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the TBPI or TBPII molecule is joined to the C terminal of the GBP 130 molecule.

4) The hybrid peptide according to daim 1 where all or part of the γlFN-R gamma interferon receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule all or part or where the N terminal of the γlFN- R molecule is joined to the C terminal of the GBP 130 molecule all or part.

5) The hybrid peptide according to daim 1 where all or part of the IL1-R interleukin high or low affinity receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule all or part or where the N terminal of the IL1-R molecule is joined to the C terminal of the GBP 130 molecule.

6) The hybrid peptide according to claim 1 where all or part of the IL2-R interleukin high or low affinity receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule all or part or where the N terminal of the IL2-R molecule is joined to the C terminal of the GBP 130 molecule.

7) The hybrid peptide according to claim 1 where all or part of the IL3-R interleukin high or low affinity receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL3-R molecule is joined to the C terminal of the GBP 130 molecule.

8) The hybrid peptide according to claim 1 where all or part of the IL4-R interleukin receptor is joined C terminally to the N tenminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL4-R molecule is joined to the C tenminal of the GBP 130 molecule.

9) The hybrid peptide according to daim 1 where all or part of the IL5-R interleukin receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL5-R molecule is joined to the C tenminal of the GBP 130 molecule.

10) The hybrid peptide according to daim 1 where all or part of the IL6-R interleukin receptor is joined C terminally to the N tenminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL6-R molecule is joined to the C tenminal of the GBP 130 molecule. 11) The hybrid peptide according to daim 1 where all or part of the IL7-R interleukin receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL7-R molecule is joined to the C terminal of the GBP 130 molecule.

12) The hybrid peptide according to daim 1 where all or part of the IL8-R interleukin receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the IL8-R molecule is joined to the C tenminal of the GBP 130 molecule.

13) The hybrid peptide according to daim 1 where all or part of the LIF-R leukaemia inhibitory fador receptor is joined C terminally to the N terminal of the GBP 130 molecule glycophorin binding peptide molecule or where the N terminal of the LIF-R molecule is joined to the C tenminal of the GBP 130 molecule.

14) The hybrid fusion peptide according to claims 1,2,3,4,5,6,7,8,9,10,11,12,13 where the malaria parasite derived peptide component is all or part of the GBPH glycophorin binding peptide homologue molecule preferably residues 70 to 427 or part of thereof joined C or N terminally to the cytokine receptor of daims 2,3,4,5,6,7,8,9,10,11,12,13.

15) The hybrid fusion peptide according to daims 1 ,2,3,4,5,6,7,8,9, 10.11.12, 13 where the malaria parasite derived peptide component is all or part of the EBA175 the erythrocyte binding antigen 175 molecule preferably residues 20 - 1435 or residues 1062 - 1103 or multiples thereof or part of thereof joined C or N terminally to the cytokine receptor of daims 2,3,4,5,6,7,8,9,10,11,12,13.

16) The hybrid fusion peptide according to daims 1,2,3,4,5,6,7,8,9,10,11,12,13 where the malaria parasite derived peptide component is all or part of the plasmodium vivax Duffy receptor molecule specially residues 23 - 1051 joined by peptide bonds to the cytokine receptor, or via chemical cross links, joined C or N terminally to the cytokine receptor of daims 2,3,4,5,6,7,8,9,10,11,12,13.

17) The hybrid fusion peptide according to daims 1,2,3,4,5,6,7,8,9,10,11,12,13 where the malaria parasite derived peptide component is all or part of the Pf200 or PMMSA malaria parasite molecule or part of thereof joined C or N terminally to the cytokine receptor of claims 2,3,4,5,6,7,8,9,10,11,12,13.

18) The hybrid fusion peptide according to daims 1,2,3,4,5,6,7,8,9,10,11,12,13 where the malaria parasite derived peptide component is all or part of the plasmodium knowiesi Duffy receptor molecule part of thereof joined C or N terminally to the cytokine receptor of daims 2,3,4,5,6,7,8,9,10,11,12,13.

19) A hybrid fusion peptide according to claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18 where a peptide sequence is interposed between the malaria parasite peptide and the cytokine receptor and where the interposed peptide is all or part of an immunoglobulin Fc molecule.

20) Protein genes encoding fusion peptides according to claims 1,2,3,4,5,6,7.8,9,10,11,12,13,14.15,16,17,18,19.

21) The fusion peptides according to claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 for use as medicine to treat and alleviate HIV 1 or HIV 2 or cerebral malaria or endotoxic shock or graft verus host disease or inflammatory disease. 22) The use of the fusion peptides according to claims 1 ,2,3,4,5,6,7,8,9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 to obtain a medicine for intended therapeutic use in the treatment of HIV 1, HIV 2, hepatitis B, pulmonary fibrosis, cerebral malaria, graft is host disease, endotoxic shock, autoimmune disease, inflammatory disease.

23) Th e f u s i o n pe ptid e s a cco rd i n g to cl a i m s 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 where the malaria parasite component is replaced all or in part by an anti-ideotype antibody or part thereof.

24) Th e f u s io n p e pti d e s a cco rd i n g to cla i m s 1 ,2,3,4,5,6,7,8,9, 10, 11 , 12, 13, 14, 15, 16, 17, 18 where the cytokine receptor is replaced by an FAB fragment or anti-ideotype.

20) The use of fusion peptides according to claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19 to obtain a medicine for intended therapeutic use as a testing kit to determine plasma levels of free plasma cytokines.

21) Th e f u s io n pepti d e s a cco rd i n g to cla i m s 1,2,3,4,5,6,7,8,9,10.11,12,13,14,15,16,17,18 and 19 where the malaria parasite component is replaced by a malaria parasite peptide derived from Plasmodium Berghei; Plasmodium Chabandi; Plasmodium Yoelei Yoelei; Plasmodium Cyanomogli; Plasmodium Gallinaceum.