CN102731650A - Monoclonal antibody for inhibiting virus from infecting human T lymphocyte - Google Patents
Monoclonal antibody for inhibiting virus from infecting human T lymphocyte Download PDFInfo
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- CN102731650A CN102731650A CN2012102083692A CN201210208369A CN102731650A CN 102731650 A CN102731650 A CN 102731650A CN 2012102083692 A CN2012102083692 A CN 2012102083692A CN 201210208369 A CN201210208369 A CN 201210208369A CN 102731650 A CN102731650 A CN 102731650A
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Abstract
The invention discloses a monoclonal antibody for inhibiting virus from infecting human T lymphocyte. The monoclonal antibody bonds with HIV-1 virus 2F5 antigenic epitope and inhibits or prevents virus from infecting human T lymphocyte. The monoclonal antibody is the one containing heavy chain variable gene VH and light chain variable gene VL sequences. The monoclonal antibody provided by the invention is provided to human body before or after human body is infected with virus and can be subjected to neutralization reaction with virus, so as to effectively inhibit or prevent virus from infecting human T lymphocyte.
Description
Technical field
The invention belongs to biological field, particularly, relate to a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body.
Background technology
The T lymphocyte derives from the multipotential stem cell (then deriving from yolk sac and liver embryonic stage) of marrow.In human embryo's phase and nascent phase, a part of multipotential stem cell or pre-T cell in the marrow are moved in the thymus gland, and differentiation and maturation under the inducing of thymine becomes and has immunocompetent T cell.The T cell is lymphocytic main ingredient; It has the various biological function; Like the direct killing target cell; Auxiliary or suppress the B cell and produce antibody, to the former responsing reaction of specific antigens and mitogenesis and produce cytokine etc., be the brave fighter who resists disease infection, tumour formation in the health.The immunne response that the T cell produces is a cellular immunization, and the effect form of cellular immunization mainly contains two kinds: combine with the target cell specificity, destroy target cell membrane, the direct killing target cell; Another kind is to discharge lymphokine, immunological effect is enlarged and enhancing.The T cell does not produce antibody, but directly works.So the immunization of T cell is called " cellular immunization ".
HIV virus is divided into 1 type and 2 types, and 1 type is the main strain of present global popular.HIV-1 is a kind of virus that can attack the human body viscera system, and as target of attack, considerable damage T4 Lymphoid tissue produces high fatefulue interior depleted most important T4 Lymphoid tissue among the human immune system for it.This virus infects in the region throughout one's life, destroys people's immunologic balance, makes human body become the carrier of various diseases.The HIV-1 body can't cause any disease, but after immunity system was destroyed by HIV, human body was because resistivity is low excessively, and the chance of immunocyte is duplicated in forfeiture, thereby the disease that infects other causes various MOI and death.Hiv virus was people's average out in intravital latent period 12 years to 13 years.
In order to prevent AIDS, consider that at first suppressing HIV-1 infects the T lymphocyte.Therefore become a very important research topic for how suppressing the virus infection T lymphocytes in human body.
Summary of the invention
Technical problem to be solved by this invention provides a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body.
The present invention solves the problems of the technologies described above the technical scheme that is adopted: a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body; This monoclonal antibody combines HIV-1 virus 2F5 epitope; Human body is suppressed or the prophylaxis of viral infections T lymphocytes in human body, and said monoclonal antibody is the monoclonal antibody that contains heavy chain variable region gene VH and chain variable region gene VL sequence.
This monoclonal antibody gives to human body before human infection virus or after human infection virus the human body administration.
Said monoclonal antibody has the aminoacid sequence and aminoacid sequence with SEQ ID NO:2 record aminoacid sequence as chain variable region gene VL of the aminoacid sequence of SEQ ID NO:1 record as heavy chain variable region gene VH.
The aminoacid sequence of said SEQ ID NO:1 record is by the gene order coding of SEQ ID NO:3 record, and the aminoacid sequence of said SEQ ID NO:2 record is by the gene order coding of SEQ ID NO:4 record.
Said monoclonal antibody has the aminoacid sequence and aminoacid sequence with SEQ ID NO:8 record aminoacid sequence as chain variable region gene VL of the aminoacid sequence of SEQ ID NO:6 record as heavy chain variable region gene VH.
The aminoacid sequence of said SEQ ID NO:6 record is by the gene order coding of SEQ ID NO:5 record, and the aminoacid sequence of said SEQ ID NO:8 record is by the gene order coding of SEQ ID NO:7 record.
In said gene sequence or the aminoacid sequence and since express after the sudden change of indivedual gene orders or aminoacid sequence, disappearance, displacement have the sequence of identical function with monoclonal antibody according to the invention, be regarded as the sequence identical with the present invention.
The invention has the beneficial effects as follows: monoclonal antibody of the present invention gives to human body before human infection virus or after human infection virus, can neutralization reaction take place with virus, effectively suppresses or the prophylaxis of viral infections T lymphocytes in human body.
Embodiment
Below in conjunction with embodiment the present invention is made further detailed description, but embodiment of the present invention is not limited only to following embodiment.
In the present embodiment; In order to suppress the infection of HIV-1 to human T cell etc.; This suppresses the monoclonal antibody of virus infection T lymphocytes in human body; This monoclonal antibody combines HIV-1 virus 2F5 epitope, and human body is suppressed or the prophylaxis of viral infections T lymphocytes in human body, and this specific antibody or fragment can suppress the infection of HIV-1 to human body; We can inject this specific antibody or fragment in human body before human body contacts HIV-1 or after the infected by HIV-1, infect thereby suppress permissive cell (for example T cell) to greatest extent.
Said monoclonal antibody is the monoclonal antibody that contains heavy chain variable region gene VH and chain variable region gene VL sequence; Particularly, be aminoacid sequence with SEQ ID NO:1 record aminoacid sequence and the aminoacid sequence of the aminoacid sequence with SEQ ID NO:2 record as chain variable region gene VL as heavy chain variable region gene VH; The aminoacid sequence of SEQ ID NO:1 record is by the gene order coding of SEQ ID NO:3 record, and the aminoacid sequence of said SEQ ID NO:2 record is by the gene order coding of SEQ ID NO:4 record.Perhaps monoclonal antibody has the aminoacid sequence and aminoacid sequence with SEQ ID NO:8 record aminoacid sequence as chain variable region gene VL of the aminoacid sequence of SEQ ID NO:6 record as heavy chain variable region gene VH; The aminoacid sequence of SEQ ID NO:6 record is by the gene order coding of SEQ ID NO:5 record, and the aminoacid sequence of said SEQ ID NO:8 record is by the gene order coding of SEQ ID NO:7 record.
The monoclonal antibody of present embodiment, variable heavy chain that has and variable sequence of light chain are shown in SEQ ID NO:1-4.Table 1 has comprised the details in fixed CDR zone.
The CDR zone of table 1. monoclonal antibody VH and VL
Another kind of antibody in the present embodiment is a kind of variable heavy chain of similar A1 antibody and monoclonal antibody of variable sequence of light chain of having, called after A2, and concrete sequence is seen SEQ ID NO:5-8.
As stated, complete antibody or fragment (for example Fab) are monoclonal antibody of the present invention.The technology for preparing above-mentioned sequence fragment and single-chain antibody belongs to known technology in this area, according to the order of above-mentioned sequence, adopt conventional sequence compound method can prepare (like the PCT amplification technique).
This invention is also included within the varient of the antibody (and fragment) that above-mentioned sequence shows; Promptly in said gene sequence or aminoacid sequence; Because that expresses after the sudden change of indivedual gene orders or aminoacid sequence, disappearance, the displacement has the sequence of identical function with monoclonal antibody according to the invention, is regarded as the sequence identical with the present invention.
According to this invention, the A1 that can be used for treating and the A2 of modified comprise IgA, IgM and IgG1, and 2,3, or A1, the variable heavy chain of A2 and 4 kinds of forms of variable light chain.
Therefore, aforesaid antibody and fragment can be formulated as a composition (for example a kind of drug ingredient).Appropriate ingredients comprises dissolving or is dispersed in the antibody (or antibody fragment) in the acceptable carrier that makes up a prescription (for example a kind of water-soluble medium).This composition can be aseptic injection form.Antibody (and fragment) also can be formulated as the composition that is fit to skin or mucous membrane topical.Such composition can be liquid, ointment, emulsifiable paste, gel and patch.
Select an acute infection patient and the patient that the similar antibody of 2F5 is arranged, set up IgM and IgG storehouse and analyze through high-flux sequence.From the IgG storehouse of an acute infection patient blood, confirmed the HIV-1 specific antibody of two time points (40 days and 8 months).These antibody are bound the envelope glycoprotein of high-affinity, but a series of 9 kinds of pseudoviruss that do not neutralize.The 40 days antibody that obtains of sampling is not present in 8 months the sample, and the antibody that obtained in the sample in 8 months not have to combine the envelope glycoprotein of giving prominence in the time of 40 days.Any antibody is not selected in the marrow translation that is derived from same patient's storehouse.
Novel antibody chooses from phage and yeast IgM+IgG demonstration storehouse, and this storehouse is derived from the patient with the similar antibody of 2F5.In these antibody, A1 has long (23 residues) heavy chain CDR3, and its variable heavy chain gene has the body sudden change of relatively low quantity.It is incorporated into the gp4l MPER polypeptide that comprises the 2F5 epitope specifically, in the cross reaction with the HIV-1 strain.
Through the HIV-1 dot matrix instrument of customization, measure stable transfection A1 supernatant antibody gene, the 293T cell cultures and connect the 2F5 epitope.Measure the serial dilution conjugated antigen epi-position of supernatant and (read average fluorescent strength-MFI).The experiment positive control comprises 2F5 mAb and HIVIG titration, and negative control is a simulation transfection supernatant.
Concrete experimental technique:
CDNA, antibody, gp140s and polypeptide
CDNA prepares with total RNA, infects after 12 months, extracts from patient's PMNC and obtains total RNA.Through the AIDS research project, obtain HIV-1 gp4l MAbs 2F5.Bo Feikang Bioisystech Co., Ltd buy to obtain reorganization gp140s from Beijing, two kinds of biotin labelings, comprises 2F5 antigen epitope sequences (2F5 polypeptide) polypeptide of determining and is used for translation and combines test: the out of order rearrangement peptide of SP62 QQEKNEQELLELDKWASLWN and SP62.Horseradish peroxidase combines anti--FLAG antibody and horseradish peroxidase to combine anti-human IgG antibody to buy for market.
The structure of Fab phage antibody library and screening
Use the cDNA that makes from patient's PMNC template as the antibody gene sequence clone; Carry out continuous translation with biotin labeling polypeptide SP62 and gp140 albumen; Preceding three-wheel translation combines magnetic bead with 1 g biotin labeling polypeptide and streptavidin; Four-wheel and the 5th is taken turns translation with gp140 (JRFL), is coated on 1 g/ hole on the ELISA thin plate in 96 holes.Combination phage on magnetic bead or the orifice plate directly is used for infecting the TGI cell that increases by index law, by M13KO7 helper phage rescue, amplifies then, is used for the next round translation.The 5th take turns translation after, 190 clones detect and on 96 orifice plates, are inoculated in the 2YT substratum, as phage E LISA examination.The positive wedding agent of confirming checks order, a novel clonal expression, and the Fab of purifying is used for preliminary evaluation.
The foundation and the selection in the phage display storehouse that light chain is reset
The Fd fragment of A1 Fab is used pcr amplification, and merges with the light chain gene sequence, and these light chain gene sequences are to be cloned on the phage vector obtaining when PCR sets up initial Fab storehouse with overlapping in essence.The chain rearranged bacterial virus storehouse packing of amplification also is kept at-80 ℃, contains among the PBS of 50% glycerine.Part deposition with a phage library; Be used for two-wheeled translation to biotin labeled MPER polypeptide; Follow by mono-clonal phage E LISA examination, as target, come the separation energy cross coupled in MPER polypeptide and the proteic clone of JRFL gp140 with JRFL gp140.
Conversion from Fab to IgGI
A1 among the plasmid pComb3X and A2 Fabs are cloned into pDR12, express when the clone back allows heavy chain and light chain.Main, the VA of heavy chain at first is cloned into pDR12 through Xbal and SacI site, and all light chain is cloned into pDR12 through HindIII and EcoRI site then.
The expression of Fab and IgGI
The HB2151 cell transformation comprises the plastid of A1Fab sequence.Single new colony is inoculated into the 2YT substratum, adds 100Ah/mL penbritin and 0.2% glucose.At 37 ℃, shaking culture under the 250rpm is up to A
600=0.5.Add sec.-propyl-L-thio-h-D-galactoside (1mmol/L) and come abduction delivering.After 30 ℃ of growths at next night, the results substratum.Bacterium under 5000g centrifugal 15 minutes is suspended among the PBS that contains polymycin B (10000units/mL) again.At room temperature cultivated 45 minutes, the Fab of solubility discharges from the cell pericentral siphon.Extract was clarified 30 minutes under 15000g, and supernatant is returned receipts, the purifying in the Nikel pipe.
A1 and A2 IgGI express in 293 free state cells, use 293Fectin to transform 293 free state cells, transform after four days, and the results culture supernatant liquid, IgGI is purifying in the a-protein row.
ELISA combines test
Antigen (streptavidin, be used for capture biotin labeling polypeptide or gp140) is coated on the aperture of 96 orifice plates, 50ng/ hole and under 4 ℃, spending the night in PBS.For phage E LISA, whenever take turns 10 in the translation
10The phage antigen inoculation.Detect with anti-M13-HRP polyclonal antibody in conjunction with phage.To the combination test of solubility Fab, anti-Flag combines HRP to be used for detecting combination.IgGI is combined ELISA, and HRP combines the goat anti-human igg antibody to be used for detecting.
The pseudovirus neutralization test
HIV-1 Envs pseudotype virus prepares through the cotransfection that 70-80%293T cell and Pnl4-3.luc.E-R and pSV7 merge, through using the polyfect transfection reagent HIV-1 Envs that encodes.After 24 hours, obtain pseudotype virus through 0.45 m filter paper filtering through centrifugal, cell culture fluid.For neutralization, the antibody of virus and different concns mixed 1 hour under 37 ℃ of conditions, and mixed solution joins about 1.5X10 then
4Among HOS-CD4-CCR5 (being applicable to all R5 and two tropic virus) or the HOS-CD4-CXCR4, cell is grown in each hole of 96 orifice plates.With luciferase detection system and microwell plate photometer measurement fluorescence, confirm to duplicate the average relative light unit (RLU) in hole after 48 hours.Inhibiting rate is calculated by following formula: [(1-comprises the average RLU in antibody hole)/have only the average RLU in viral hole] * 100%.
Neutralization test based on PMNC
Measure the HIV-1 neutralization in the PMNC test, as the reduction of repeatedly duplicating back LucR reporter gene expression in virus.Virus inoculation is 150 l at TV, comprises in the growth medium of IL-2 in the test specimens (coming to 8 times of dilutions) of a series of 3 times of dilutions, is duplicating one hour under 37 ℃ of conditions on the culture plate at the bottom of the U-shaped in one 96 hole.The PHA-PMNC s (2X10 of an age in days is all added in every hole
5Individual cell at 50 l, comprise in the growth medium of IL-2).One group of control wells is added with the cell (virus control) of virus, and another group only adds cell (background contrast).Cultivate after four days, on 100 l cell transfer to, the 96 hole white solid thin plate (Costar), it is luminous to be used to use ViviRen viable cell matrix (Promega) to measure the Renilla luciferase.
454 order-checkings from the entire I gG of the VH gene order of patient SC44
From the segmental IgG of Fd with isolated cDNA in the patient body as template through pcr amplification, used aforesaid primer.Antisense primer is IgGR (5 '-ACTAG TTTTGTCACAAGATTTGGGCTCAACTBTCTTGTCCACCTTGGTGTTGC-3 '), and all IgGI-4 have this.PCR carries out 25 in the container of one 50 l takes turns.This product is a gel-purified; Then as the template of pcr amplification for the second time, increase specifically 12 take turns and with comprise 454 check order special joints primer (HF12:5'-CCATCTCATCCCTGCGTGTCTCCGACTCAGTACTGAGCTAGCTGCCCA ACCAGCCATGGCC-3 ' and HR2:5'CCTATC CCCTGTGTGCCTTGGCAGTCTCAGGTCACAAGATTTGGGCTCAAC-3 ').The product that obtains is a gel-purified, is used for 454 order-checkings, and is consistent with the sequence of describing.
Be directed against the similar research of the VH gene order that obtains through 454 order-checkings with A1 VH and sexual cell V gene fragment
Through each database entry utilization standard P erl String::Similarity module (CPAN String-Similarity-1.04 by Marc Lehmann) being obtained the similar coupling of A1 VH, sexual cell probe and SC44 VH gene order.Through continuously zero position 1-n utilization String::Similarity algorithm being obtained the single best scoring relatively of each sequence.The scoring that is below or above selected threshold value (similar per-cent) remains the analysis that is used for the back.
The result
Separation and the affinity maturation of A1 through the phage display storehouse
After taking turns to MPER polypeptide and gp140 albumen translation 5,190 at random clone body detect and be used for the mono-clonal phage selection.Sequential analysis through definite positive colony shows that the sequence of A1 is shown in SEQ ID NO:1.A1 VH has 8 sudden changes from VH51-1 V gene in its heavy chain V gene fragment; A1VL has 3 sudden changes from VK-1-39 in its light chain V gene fragment.Contrast 2F5 and 4E10, A1 VH and VL experience the sudden change of quite low quantity in their reproductive process, this shows that A1 still is in the commitment of antibody ripening process.According to observations, heavy chain CDR3 has 23 residues and a plurality of tyrosine and a phenylalanine(Phe).
In order further to improve the binding affinity of A1, having set up aforesaid size is 2*10
8Light chain reset the storehouse.A chain data rearrangement storehouse is to MPER polypeptide translation two-wheeled, and carrying out subsequently with gp140 is the phage E LISA screening of target.Determine 6 unique clones, between these 2 clones identical heavy chain is arranged, but match with different light chains from several places sudden change of having of identical VL subtribe.The ELISA data presentation, similar, they all combine polypeptide and gp140 well.In these 6 clones, a light chain V gene fragment has the clone body of 9 sudden changes to be designated as A2, and is converted into IgGI and is used for further evaluation.
The neutralization of A1 Fab and IgGI is active
Through measuring A1 and the A2 IgG neutrality for virus, the result shows, A1, and the neutrality of A2 significantly increases.
Table 2. is to a series of HIV bacterial strains, among A1 and the A2 and the activity experiment result
Strengthen neutralization by the receptor-mediated A2 IgGI of FcyRl
In neutralization test, when FcyRl expresses in target cell equally, extensively for example 2F5 and 4E10 of neutralizing antibody is target with the MPER zone, can be to infect with pseudovirus in the very high potentiality.In order to detect A1 whether same characteristic is arranged also, same neutralization activity of in the TZM-bl/FcyRI cell, testing A2 IgGI, A1 Fab and a kind of incoherent antibody m102.4 are with comparing.In the table 3 data presented show A2 IgGI in increased by 1000 times with potentiality, yet do not observe growth in the A1 Fab contrast, showing increases substantially gives the credit to the Fc part of A2 IgGI and in the combination of the FcyRI of target cell surface over-expresses.
Effective neutralization that table 3. TZM-bl/FcyRI cell infects the HIV pseudovirus
Threshold value is the concentration (ug/ml) that relative light unit (RLUs) reduces at 50% o'clock than virus control lattice (not having test specimens).
Can know by above-mentioned experimental result; Through before human body contact HIV-1 or after the infected by HIV-1, in human body, injecting monoclonal antibody of the present invention (fragment); Perhaps comprise compsn, medicine of this monoclonal antibody etc.; Can effectively suppress the infection of HIV-1, thereby suppress the virus infection T lymphocytes in human body to greatest extent human body.
As stated, just can realize the present invention preferably.
< 110>Sichuan remittance space pharmaceutical Co. Ltd
< 120>a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body
< 130>a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body
<160> 8
<170> PatentIn?version?3.3
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<212> PRT
< 213>artificial sequence
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Gln?Met?Gln?Leu?Val?Gln?Ser?Gly?Ala?Glu?Val?Lys?Lys?Pro?Gly?Glu
1 5 10 15
Ser?Leu?Lys?Ile?Ser?Cys?Lys?Val?Ser?Gly?Tyr?Asn?Phe?Ala?Ser?Glu
20 25 30
Trp?Ile?Gly?Trp?Val?Arg?Gln?Met?Pro?Gly?Lys?Gly?Leu?Glu?Trp?Met
35 40 45
Gly?Ile?Ile?Tyr?Pro?Gly?Asp?Ser?Asp?Thr?Lys?Tyr?Ser?Pro?Ser?Phe
50 55 60
Gln?Gly?Gln?Val?Ile?Ile?Ser?Ala?Asp?Lys?Ser?Ile?Asn?Thr?Ala?Tyr
65 70 75 80
Leu?Gln?Trp?Ser?Ser?Leu?Lys?Ala?Ser?Asp?Thr?Ala?Ile?Tyr?Tyr?Cys
85 90 95
Ala?Arg?Gln?Asn?His?Tyr?Gly?Ser?Gly?Ser?Tyr?Phe?Tyr?Arg?Thr?Ala
100 105 110
Tyr?Tyr?Tyr?Ala?Met?Asp?Val?Trp?Gly?Gln?Gly?Thr?Thr?Val?Thr?Val
115 120 125
Ser?Ser
130
<210> 2
<211> 113
<212> PRT
< 213>artificial sequence
<400> 2
Val?Ala?Gln?Ala?Ala?Asp?Ile?Gln?Leu?Thr?Gln?Ser?Pro?Ser?Ser?Leu
1 5 10 15
Ser?Ala?Ser?Val?Gly?Asp?Arg?Val?Thr?Ile?Thr?Cys?Arg?Ala?Ser?Gln
20 25 30
Ser?Ile?Ser?Ser?Tyr?Leu?Asn?Trp?Tyr?Gln?Gln?Lys?Pro?Gly?Lys?Ala
35 40 45
Pro?Asn?Leu?Leu?Ile?Tyr?Ala?Ala?Ser?Ser?Leu?Gln?Ser?Gly?Val?Pro
50 55 60
Ser?Arg?Phe?Ser?Gly?Ser?Gly?Ser?Gly?Thr?Asp?Phe?Thr?Leu?Thr?Ile
65 70 75 80
Ser?Ser?Leu?Gln?Pro?Glu?Asp?Phe?Ala?Thr?Tyr?Tyr?Cys?Gln?Gln?Ser
85 90 95
Tyr?Asn?Thr?Pro?Phe?Thr?Leu?Gly?Pro?Gly?Thr?Lys?Val?Glu?Ile?Lys
100 105 110
Arg
<210> 3
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<212> DNA
< 213>artificial sequence
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cagatgcagc?tggtgcagtc?tggagcagag?gtgaaaaagc?ccggggagtc?tctgaagatc 60
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<210> 4
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<212> DNA
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ttcactcttg?gcccggggac?caaggtggag?atcaaa 336
<210> 5
<211> 390
<212> DNA
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cagatgcagc?tggtgcagtc?tggagcagag?gtgaaaaagc?ccggggagtc?tctgaagatc 60
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cccgggaaag?gcccggagtg?gatggggatt?atctatcctg?gtgactctga?taccaaatac 180
agcccgtcct?tccaaggcca?ggtcatcatc?tcagccgaca?agtccatcaa?caccgcctac 240
ctgcagtgga?gcagcctgaa?ggcctcggac?accgccatat?attactgtgc?gagacagaat 300
cactatggtt?cggggagtta?tttctaccga?acggcctact?actatgctat?ggacgtctgg 360
ggccaaggga?ccacggtcac?cgtctcctca 390
<210> 6
<211> 130
<212> PRT
< 213>artificial sequence
<400> 6
Gln?Met?Gln?Leu?Val?Gln?Ser?Gly?Ala?Glu?Val?Lys?Lys?Pro?Gly?Glu
1 5 10 15
Ser?Leu?Lys?Ile?Ser?Cys?Lys?Val?Ser?Gly?Tyr?Asn?Phe?Ala?Ser?Glu
20 25 30
Trp?Ile?Gly?Trp?Val?Arg?Gln?Met?Pro?Gly?Lys?Gly?Leu?Glu?Trp?Met
35 40 45
Gly?Ile?Ile?Tyr?Pro?Gly?Asp?Ser?Asp?Thr?Lys?Tyr?Ser?Pro?Ser?Phe
50 55 60
Gln?Gly?Gln?Val?Ile?Ile?Ser?Ala?Asp?Lys?Ser?Ile?Asn?Thr?Ala?Tyr
65 70 75 80
Leu?Gln?Trp?Ser?Ser?Leu?Lys?Ala?Ser?Asp?Thr?Ala?Ile?Tyr?Tyr?Cys
85 90 95
Ala?Arg?Gln?Asn?His?Tyr?Gly?Ser?Gly?Ser?Tyr?Phe?Tyr?Arg?Thr?Ala
100 105 110
Tyr?Tyr?Tyr?Ala?Met?Asp?Val?Trp?Gly?Gln?Gly?Thr?Thr?Val?Thr?Val
115 120 125
Ser?Ser
130
<210> 7
<211> 324
<212> DNA
< 213>artificial sequence
<400> 7
gacatccagt?tgacccagtc?tccatcttcc?ctgtctgcat?ctttggggga?caaagtcacc 60
atcacttgcc?gggcaagtca?gcacattaag?aagtatttaa?actggtatca?gcagaaacct 120
gggaaagccc?ctaaactcct?gatctatggt?gcactcaatt?tgcagagtgg?ggtcccatca 180
aggttcagtg?gcagaggatc?tgggacagat?ttcactccca?ccatcagcag?tctgcaacct 240
gaagattttg?caacttacta?ctgtcagcag?agttacagta?ccccattcac?ttccggccct 300
gggaccaaag?tggatatcaa?acga 324
<210> 8
<211> 108
<212> PRT
< 213>artificial sequence
<400> 8
Asp?Ile?Gln?Leu?Thr?Gln?Ser?Pro?Ser?Ser?Leu?Ser?Ala?Ser?Leu?Gly
1 5 10 15
Asp?Lys?Val?Thr?Ile?Thr?Cys?Arg?Ala?Ser?Gln?His?Ile?Lys?Lys?Tyr
20 25 30
Leu?Asn?Trp?Tyr?Gln?Gln?Lys?Pro?Gly?Lys?Ala?Pro?Lys?Leu?Leu?Ile
35 40 45
Tyr?Gly?Ala?Leu?Asn?Leu?Gln?Ser?Gly?Val?Pro?Ser?Arg?Phe?Ser?Gly
50 55 60
Arg?Gly?Ser?Gly?Thr?Asp?Phe?Thr?Leu?Thr?Ile?Ser?Ser?Leu?Gln?Pro
65 70 75 80
Glu?Asp?Phe?Ala?Thr?Tyr?Tyr?Cys?Gln?Gln?Ser?Tyr?Ser?Thr?Pro?Phe
85 90 95
Thr?Phe?Gly?Pro?Gly?Thr?Lys?Val?Asp?Ile?Lys?Arg
100 105
Claims (6)
1. monoclonal antibody that suppresses the virus infection T lymphocytes in human body; It is characterized in that: this monoclonal antibody combines HIV-1 virus 2F5 epitope; Human body is suppressed or the prophylaxis of viral infections T lymphocytes in human body, and said monoclonal antibody is the monoclonal antibody that contains heavy chain variable region gene VH and chain variable region gene VL sequence.
2. a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body according to claim 1, it is characterized in that: monoclonal antibody gives to human body before human infection virus or after human infection virus the human body administration.
3. a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body according to claim 1 and 2 is characterized in that: said monoclonal antibody has the aminoacid sequence and aminoacid sequence with SEQ ID NO:2 record aminoacid sequence as chain variable region gene VL of the aminoacid sequence of SEQ ID NO:1 record as heavy chain variable region gene VH.
4. a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body according to claim 3; It is characterized in that: the aminoacid sequence of said SEQ ID NO:1 record is by the gene order coding of SEQ ID NO:3 record, and the aminoacid sequence of said SEQ ID NO:2 record is by the gene order coding of SEQ ID NO:4 record.
5. a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body according to claim 1 and 2 is characterized in that: said monoclonal antibody has the aminoacid sequence and aminoacid sequence with SEQ ID NO:8 record aminoacid sequence as chain variable region gene VL of the aminoacid sequence of SEQ ID NO:6 record as heavy chain variable region gene VH.
6. a kind of monoclonal antibody that suppresses the virus infection T lymphocytes in human body according to claim 5; It is characterized in that: the aminoacid sequence of said SEQ ID NO:6 record is by the gene order coding of SEQ ID NO:5 record, and the aminoacid sequence of said SEQ ID NO:8 record is by the gene order coding of SEQ ID NO:7 record.
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| CN2012102083692A CN102731650A (en) | 2012-06-21 | 2012-06-21 | Monoclonal antibody for inhibiting virus from infecting human T lymphocyte |
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| CN2012102083692A CN102731650A (en) | 2012-06-21 | 2012-06-21 | Monoclonal antibody for inhibiting virus from infecting human T lymphocyte |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101716350A (en) * | 2009-10-29 | 2010-06-02 | 哈尔滨医科大学 | AIDS live carrier multipartial vaccine and construction method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101716350A (en) * | 2009-10-29 | 2010-06-02 | 哈尔滨医科大学 | AIDS live carrier multipartial vaccine and construction method thereof |
Non-Patent Citations (3)
| Title |
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| ZHU,Z ET AL: "ACCESSION NO：AEO11810，2F5-like anti-HIV immunoglobulin heavy chain variable region", 《GENBANK DATABASE》 * |
| ZHU,Z ET AL: "ACCESSION NO：AEO11811，2F5-like anti-HIV immunoglobulin light chain variable region", 《GENBANK DATABASE》 * |
| ZHU,Z ET AL: "ACCESSION NO：AEO11812，2F5-like anti-HIV immunoglobulin light chain variable region", 《GENBANK DATABASE》 * |
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