DE69320967T2 - Unterdrückung der t-zell proliferation mittels peptidfragmenten des myelin basischen protein - Google Patents
Unterdrückung der t-zell proliferation mittels peptidfragmenten des myelin basischen proteinInfo
- Publication number
- DE69320967T2 DE69320967T2 DE69320967T DE69320967T DE69320967T2 DE 69320967 T2 DE69320967 T2 DE 69320967T2 DE 69320967 T DE69320967 T DE 69320967T DE 69320967 T DE69320967 T DE 69320967T DE 69320967 T2 DE69320967 T2 DE 69320967T2
- Authority
- DE
- Germany
- Prior art keywords
- mbp
- cells
- cell
- peptide
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000001629 suppression Effects 0.000 title description 69
- 108010033276 Peptide Fragments Proteins 0.000 title description 11
- 102000007079 Peptide Fragments Human genes 0.000 title description 11
- 230000006052 T cell proliferation Effects 0.000 title description 9
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 188
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 17
- 125000000539 amino acid group Chemical group 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
- 239000012634 fragment Substances 0.000 abstract description 65
- 102000004196 processed proteins & peptides Human genes 0.000 abstract description 65
- 230000006472 autoimmune response Effects 0.000 abstract description 6
- 125000001433 C-terminal amino-acid group Chemical group 0.000 abstract description 2
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 abstract description 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 abstract 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 335
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 306
- 102000047918 Myelin Basic Human genes 0.000 description 219
- 101710107068 Myelin basic protein Proteins 0.000 description 219
- 210000004027 cell Anatomy 0.000 description 121
- 239000000427 antigen Substances 0.000 description 114
- 108091007433 antigens Proteins 0.000 description 111
- 102000036639 antigens Human genes 0.000 description 111
- 201000006417 multiple sclerosis Diseases 0.000 description 80
- 238000000034 method Methods 0.000 description 59
- 108091008874 T cell receptors Proteins 0.000 description 52
- 201000002491 encephalomyelitis Diseases 0.000 description 51
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 49
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 47
- 241001465754 Metazoa Species 0.000 description 43
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 42
- 101001018318 Homo sapiens Myelin basic protein Proteins 0.000 description 39
- 210000000612 antigen-presenting cell Anatomy 0.000 description 39
- 102000054064 human MBP Human genes 0.000 description 39
- 230000000638 stimulation Effects 0.000 description 39
- 201000010099 disease Diseases 0.000 description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 37
- 102000000588 Interleukin-2 Human genes 0.000 description 36
- 108010002350 Interleukin-2 Proteins 0.000 description 36
- 230000009257 reactivity Effects 0.000 description 36
- 230000035755 proliferation Effects 0.000 description 34
- 108090000623 proteins and genes Proteins 0.000 description 34
- 230000004044 response Effects 0.000 description 34
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 33
- 230000001712 encephalitogenic effect Effects 0.000 description 32
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 31
- 230000006698 induction Effects 0.000 description 30
- 210000003719 b-lymphocyte Anatomy 0.000 description 26
- 235000001014 amino acid Nutrition 0.000 description 22
- 230000007246 mechanism Effects 0.000 description 22
- 229940024606 amino acid Drugs 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 20
- 238000001990 intravenous administration Methods 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 20
- 150000001413 amino acids Chemical class 0.000 description 19
- 210000004989 spleen cell Anatomy 0.000 description 19
- 238000012546 transfer Methods 0.000 description 19
- 230000000694 effects Effects 0.000 description 18
- 238000011282 treatment Methods 0.000 description 17
- 238000002474 experimental method Methods 0.000 description 16
- 241000124008 Mammalia Species 0.000 description 15
- 241000700159 Rattus Species 0.000 description 15
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 15
- 230000001506 immunosuppresive effect Effects 0.000 description 15
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 15
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 15
- 230000008004 immune attack Effects 0.000 description 14
- 230000001939 inductive effect Effects 0.000 description 14
- 239000002609 medium Substances 0.000 description 14
- 235000018102 proteins Nutrition 0.000 description 14
- 102000004169 proteins and genes Human genes 0.000 description 14
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 13
- 102000004388 Interleukin-4 Human genes 0.000 description 13
- 108090000978 Interleukin-4 Proteins 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 238000007792 addition Methods 0.000 description 12
- 229940028885 interleukin-4 Drugs 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 11
- 241000282412 Homo Species 0.000 description 10
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 10
- 239000000443 aerosol Substances 0.000 description 10
- 230000006470 autoimmune attack Effects 0.000 description 10
- 210000003169 central nervous system Anatomy 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 230000005951 type IV hypersensitivity Effects 0.000 description 10
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 10
- 208000023275 Autoimmune disease Diseases 0.000 description 9
- 102000055324 Myelin Proteolipid Human genes 0.000 description 9
- 108700021862 Myelin Proteolipid Proteins 0.000 description 9
- 230000028993 immune response Effects 0.000 description 9
- 210000005259 peripheral blood Anatomy 0.000 description 9
- 239000011886 peripheral blood Substances 0.000 description 9
- 230000004043 responsiveness Effects 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 230000020192 tolerance induction in gut-associated lymphoid tissue Effects 0.000 description 9
- 241000700199 Cavia porcellus Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 210000005087 mononuclear cell Anatomy 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 206010062016 Immunosuppression Diseases 0.000 description 7
- 108091054438 MHC class II family Proteins 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000003053 immunization Effects 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 210000002540 macrophage Anatomy 0.000 description 7
- 230000001537 neural effect Effects 0.000 description 7
- 238000003752 polymerase chain reaction Methods 0.000 description 7
- 230000011664 signaling Effects 0.000 description 7
- 208000012902 Nervous system disease Diseases 0.000 description 6
- 208000025966 Neurological disease Diseases 0.000 description 6
- 238000002105 Southern blotting Methods 0.000 description 6
- 101001018322 Sus scrofa Myelin basic protein Proteins 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000000981 bystander Effects 0.000 description 6
- 238000001516 cell proliferation assay Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000139 costimulatory effect Effects 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000002158 endotoxin Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 238000011694 lewis rat Methods 0.000 description 6
- 229920006008 lipopolysaccharide Polymers 0.000 description 6
- 238000002595 magnetic resonance imaging Methods 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 108010062580 Concanavalin A Proteins 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 102000043131 MHC class II family Human genes 0.000 description 5
- 241001529936 Murinae Species 0.000 description 5
- 230000017274 T cell anergy Effects 0.000 description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 102000054766 genetic haplotypes Human genes 0.000 description 5
- 210000002443 helper t lymphocyte Anatomy 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002372 labelling Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- 239000012747 synergistic agent Substances 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 241000699660 Mus musculus Species 0.000 description 4
- 230000006044 T cell activation Effects 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 238000010370 cell cloning Methods 0.000 description 4
- 230000003915 cell function Effects 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 230000001066 destructive effect Effects 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- GZQKNULLWNGMCW-PWQABINMSA-N lipid A (E. coli) Chemical compound O1[C@H](CO)[C@@H](OP(O)(O)=O)[C@H](OC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCCCC)[C@@H](NC(=O)C[C@@H](CCCCCCCCCCC)OC(=O)CCCCCCCCCCC)[C@@H]1OC[C@@H]1[C@@H](O)[C@H](OC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](NC(=O)C[C@H](O)CCCCCCCCCCC)[C@@H](OP(O)(O)=O)O1 GZQKNULLWNGMCW-PWQABINMSA-N 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 210000002418 meninge Anatomy 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000010532 solid phase synthesis reaction Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 108010033040 Histones Proteins 0.000 description 3
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 3
- 101001100327 Homo sapiens RNA-binding protein 45 Proteins 0.000 description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- 238000012408 PCR amplification Methods 0.000 description 3
- 102000003923 Protein Kinase C Human genes 0.000 description 3
- 108090000315 Protein Kinase C Proteins 0.000 description 3
- 102000016202 Proteolipids Human genes 0.000 description 3
- 108010010974 Proteolipids Proteins 0.000 description 3
- 102100038823 RNA-binding protein 45 Human genes 0.000 description 3
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 3
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000000735 allogeneic effect Effects 0.000 description 3
- 230000030741 antigen processing and presentation Effects 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 238000010804 cDNA synthesis Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000036737 immune function Effects 0.000 description 3
- 230000004957 immunoregulator effect Effects 0.000 description 3
- PNDZEEPOYCVIIY-UHFFFAOYSA-N indo-1 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C=2N=C3[CH]C(=CC=C3C=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 PNDZEEPOYCVIIY-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000003226 mitogen Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- 101150084750 1 gene Proteins 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 208000016192 Demyelinating disease Diseases 0.000 description 2
- 206010012305 Demyelination Diseases 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010058597 HLA-DR Antigens Proteins 0.000 description 2
- 102000006354 HLA-DR Antigens Human genes 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 2
- 101001018320 Mus musculus Myelin basic protein Proteins 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 108010038807 Oligopeptides Proteins 0.000 description 2
- 102000015636 Oligopeptides Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000005859 cell recognition Effects 0.000 description 2
- 230000005754 cellular signaling Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000004940 costimulation Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 238000005304 joining Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- MIKKOBKEXMRYFQ-WZTVWXICSA-N meglumine amidotrizoate Chemical compound C[NH2+]C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I MIKKOBKEXMRYFQ-WZTVWXICSA-N 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229940071648 metered dose inhaler Drugs 0.000 description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 2
- 229960000951 mycophenolic acid Drugs 0.000 description 2
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 210000000578 peripheral nerve Anatomy 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000009696 proliferative response Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 230000007781 signaling event Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 231100000617 superantigen Toxicity 0.000 description 2
- 230000002992 thymic effect Effects 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 230000024664 tolerance induction Effects 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- UHEPSJJJMTWUCP-DHDYTCSHSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-[(1r)-1-hydroxyethyl]oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H]([C@@H](C)O)O2)N)[C@@H](N)C[C@H]1N UHEPSJJJMTWUCP-DHDYTCSHSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 1
- 102000006306 Antigen Receptors Human genes 0.000 description 1
- 108010083359 Antigen Receptors Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 108010045634 B7 Antigens Proteins 0.000 description 1
- 102000005738 B7 Antigens Human genes 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 101001018362 Bos taurus Myelin basic protein Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 108010084313 CD58 Antigens Proteins 0.000 description 1
- 241000744472 Cinna Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 101150082328 DRB5 gene Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
- LLEUXCDZPQOJMY-AAEUAGOBSA-N Glu-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCC(O)=O)N)C(O)=O)=CNC2=C1 LLEUXCDZPQOJMY-AAEUAGOBSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000015789 HLA-DP Antigens Human genes 0.000 description 1
- 108010010378 HLA-DP Antigens Proteins 0.000 description 1
- 108010064885 HLA-DR3 Antigen Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 101100400614 Homo sapiens MBP gene Proteins 0.000 description 1
- 101001013648 Homo sapiens Methionine synthase Proteins 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 101000759926 Homo sapiens Ubiquitin carboxyl-terminal hydrolase isozyme L1 Proteins 0.000 description 1
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
- 102000000521 Immunophilins Human genes 0.000 description 1
- 108010016648 Immunophilins Proteins 0.000 description 1
- 206010021639 Incontinence Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000019687 Lamb Nutrition 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 208000035032 Multiple sulfatase deficiency Diseases 0.000 description 1
- 101100096028 Mus musculus Smok1 gene Proteins 0.000 description 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 101100117569 Oryza sativa subsp. japonica DRB6 gene Proteins 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 206010033892 Paraplegia Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 1
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 206010037714 Quadriplegia Diseases 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 101001018324 Rattus norvegicus Myelin basic protein Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- -1 Steroid compounds Chemical class 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 230000027526 T cell tolerance induction Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 210000004241 Th2 cell Anatomy 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100025038 Ubiquitin carboxyl-terminal hydrolase isozyme L1 Human genes 0.000 description 1
- 101150117115 V gene Proteins 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000007503 antigenic stimulation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000000599 auto-anti-genic effect Effects 0.000 description 1
- 238000000211 autoradiogram Methods 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- YTRQFSDWAXHJCC-UHFFFAOYSA-N chloroform;phenol Chemical compound ClC(Cl)Cl.OC1=CC=CC=C1 YTRQFSDWAXHJCC-UHFFFAOYSA-N 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 238000011509 clonal analysis Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960000633 dextran sulfate Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000000147 enterotoxin Substances 0.000 description 1
- 231100000655 enterotoxin Toxicity 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 210000000285 follicular dendritic cell Anatomy 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 239000000185 hemagglutinin Substances 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 208000010726 hind limb paralysis Diseases 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000037189 immune system physiology Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002998 immunogenetic effect Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940073062 imuran Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002664 langerhans' cell Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000000207 lymphocyte subset Anatomy 0.000 description 1
- 239000006249 magnetic particle Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006033 mucosulfatidosis Diseases 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 108010087487 myelin basic protein 85-99 Proteins 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000036279 refractory period Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002047 thymogen Effects 0.000 description 1
- 108010014252 thymogen Proteins 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4713—Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Biomedical Technology (AREA)
- Rehabilitation Therapy (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86531892A | 1992-04-09 | 1992-04-09 | |
| PCT/US1993/003369 WO1993021222A1 (en) | 1992-04-09 | 1993-04-09 | Suppression of t-cell proliferation using peptide fragments of myelin basic protein |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69320967D1 DE69320967D1 (de) | 1998-10-15 |
| DE69320967T2 true DE69320967T2 (de) | 1999-05-12 |
Family
ID=25345228
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69331501T Expired - Lifetime DE69331501T2 (de) | 1992-04-09 | 1993-04-09 | Unterdrückung der Proliferation von T-Zellen mittels Peptidfragmenten des basischen Proteins aus Myelin |
| DE69320967T Expired - Lifetime DE69320967T2 (de) | 1992-04-09 | 1993-04-09 | Unterdrückung der t-zell proliferation mittels peptidfragmenten des myelin basischen protein |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69331501T Expired - Lifetime DE69331501T2 (de) | 1992-04-09 | 1993-04-09 | Unterdrückung der Proliferation von T-Zellen mittels Peptidfragmenten des basischen Proteins aus Myelin |
Country Status (15)
| Country | Link |
|---|---|
| EP (2) | EP0863155B1 (enExample) |
| JP (1) | JP3434510B2 (enExample) |
| KR (1) | KR950700934A (enExample) |
| AT (2) | ATE212358T1 (enExample) |
| AU (1) | AU680824B2 (enExample) |
| BR (1) | BR9306272A (enExample) |
| CA (1) | CA2133749A1 (enExample) |
| DE (2) | DE69331501T2 (enExample) |
| DK (1) | DK0863155T3 (enExample) |
| ES (1) | ES2172044T3 (enExample) |
| HU (1) | HU219306B (enExample) |
| IL (1) | IL105347A0 (enExample) |
| NO (1) | NO317049B1 (enExample) |
| PT (1) | PT863155E (enExample) |
| WO (1) | WO1993021222A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5869054A (en) * | 1987-06-24 | 1999-02-09 | Autoimmune Inc. | Treatment of multiple sclerosis by oral administration of autoantigens |
| US5817629A (en) * | 1991-10-22 | 1998-10-06 | The Governors Of The University Of Alberta | Peptide specificity of anti-myelin basic protein and the administration of myelin basic protein peptides to multiple sclerosis patients |
| US6252040B1 (en) | 1991-10-22 | 2001-06-26 | The Governors Of The University Of Alberta | Peptide specificity of anti-myelin basic protein and the administration of myelin basic protein peptides to multiple sclerosis patients |
| HUT76099A (en) * | 1994-05-10 | 1997-06-30 | Immulogic Pharma Corp | Compositions and treatment for multiple sclerosis |
| PL324091A1 (en) * | 1994-10-25 | 1998-05-11 | Immulogic Pharma Corp | Compositions and procedure for treating sclerosis multiplex |
| US6251396B1 (en) | 1994-11-18 | 2001-06-26 | Neurocrine Biosciences, Inc. | Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein |
| US6329499B1 (en) * | 1994-11-18 | 2001-12-11 | Neurocrine Biosciences, Inc. | Methods for treatment of multiple sclerosis using peptide analogues of human myelin basic protein |
| JPH10509714A (ja) | 1994-11-18 | 1998-09-22 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | ヒトミエリン塩基性タンパク質の９１位におけるペプチドアナログを用いる多発性硬化症の処置方法 |
| US6379670B1 (en) | 1994-11-18 | 2002-04-30 | Neurocrine Biosciences, Inc. | Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein |
| WO1996028470A2 (en) * | 1995-03-09 | 1996-09-19 | Neurocrine Biosciences, Inc. | Peptide analogues of human myelin basic protein useful in treating multiple sclerosis |
| US5856446A (en) * | 1995-07-07 | 1999-01-05 | Autoimmune Inc. | Method of treating rheumatoid arthritis with low dose type II collagen |
| IL116559A (en) * | 1995-11-17 | 2005-11-20 | Yissum Res Dev Co | Chimeric protein consisting of a bacterial toxin and a myelin basic protein sequence |
| US6274136B1 (en) * | 1996-05-29 | 2001-08-14 | University Of Southern California | Construction and use of genes encoding pathogenic epitopes for treatment of autoimmune disease |
| CA2201841C (en) * | 1997-04-04 | 2010-01-26 | The Governors Of The University Of Alberta | Peptide specificity of anti-myelin basic protein and the administration of myelin basic protein peptides to multiple sclerosis patients |
| US20020072493A1 (en) | 1998-05-19 | 2002-06-13 | Yeda Research And Development Co. Ltd. | Activated T cells, nervous system-specific antigens and their uses |
| EP1080110A2 (en) * | 1998-05-19 | 2001-03-07 | Yeda Research And Development Co. Ltd. | Use of activated t cells, nervous system-specific antigens for treating disorders of the nevrous system |
| US7261896B2 (en) | 2000-05-24 | 2007-08-28 | United States Of America As Represented By The Secretary Of The Department Of Health And Human Services National Institutes Of Health | Methods for preventing strokes by inducing tolerance to e-selectin |
| US20080107664A1 (en) | 2003-10-17 | 2008-05-08 | Zang Ying C Q | Method For Increasing Cd8+ Cytotoxic T Cell Responses And For Treating Multiple Sclerosis |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995008572A1 (en) * | 1993-09-22 | 1995-03-30 | The Board Of Trustees For The Leland Stanford Junior University | Interaction of t-cell receptors and antigen in autoimmune disease |
| JPH10509714A (ja) * | 1994-11-18 | 1998-09-22 | ニューロクライン バイオサイエンシーズ， インコーポレイテッド | ヒトミエリン塩基性タンパク質の９１位におけるペプチドアナログを用いる多発性硬化症の処置方法 |
-
1993
- 1993-04-09 AT AT98102522T patent/ATE212358T1/de not_active IP Right Cessation
- 1993-04-09 DE DE69331501T patent/DE69331501T2/de not_active Expired - Lifetime
- 1993-04-09 AU AU42824/93A patent/AU680824B2/en not_active Ceased
- 1993-04-09 BR BR9306272A patent/BR9306272A/pt not_active Application Discontinuation
- 1993-04-09 IL IL105347A patent/IL105347A0/xx unknown
- 1993-04-09 WO PCT/US1993/003369 patent/WO1993021222A1/en not_active Ceased
- 1993-04-09 PT PT98102522T patent/PT863155E/pt unknown
- 1993-04-09 EP EP98102522A patent/EP0863155B1/en not_active Expired - Lifetime
- 1993-04-09 AT AT93912176T patent/ATE170874T1/de not_active IP Right Cessation
- 1993-04-09 JP JP51850993A patent/JP3434510B2/ja not_active Expired - Fee Related
- 1993-04-09 CA CA002133749A patent/CA2133749A1/en not_active Abandoned
- 1993-04-09 ES ES98102522T patent/ES2172044T3/es not_active Expired - Lifetime
- 1993-04-09 DE DE69320967T patent/DE69320967T2/de not_active Expired - Lifetime
- 1993-04-09 EP EP93912176A patent/EP0650498B1/en not_active Expired - Lifetime
- 1993-04-09 HU HU9402909A patent/HU219306B/hu not_active IP Right Cessation
- 1993-04-09 DK DK98102522T patent/DK0863155T3/da active
-
1994
- 1994-10-06 NO NO19943755A patent/NO317049B1/no not_active IP Right Cessation
- 1994-10-08 KR KR1019940703571A patent/KR950700934A/ko active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| ATE212358T1 (de) | 2002-02-15 |
| KR950700934A (ko) | 1995-02-20 |
| ATE170874T1 (de) | 1998-09-15 |
| JP3434510B2 (ja) | 2003-08-11 |
| WO1993021222A1 (en) | 1993-10-28 |
| DE69331501D1 (de) | 2002-03-14 |
| DE69320967D1 (de) | 1998-10-15 |
| HUT69169A (en) | 1995-08-28 |
| KR100295606B1 (enExample) | 2001-10-22 |
| DE69331501T2 (de) | 2002-08-29 |
| BR9306272A (pt) | 1998-06-23 |
| CA2133749A1 (en) | 1993-10-28 |
| EP0650498B1 (en) | 1998-09-09 |
| NO317049B1 (no) | 2004-07-26 |
| HU219306B (en) | 2001-03-28 |
| AU4282493A (en) | 1993-11-18 |
| EP0650498A1 (en) | 1995-05-03 |
| IL105347A0 (en) | 1993-08-18 |
| PT863155E (pt) | 2002-07-31 |
| NO943755L (no) | 1994-12-02 |
| DK0863155T3 (da) | 2002-05-13 |
| AU680824B2 (en) | 1997-08-14 |
| EP0650498A4 (en) | 1995-06-21 |
| NO943755D0 (no) | 1994-10-06 |
| EP0863155A1 (en) | 1998-09-09 |
| HU9402909D0 (en) | 1995-01-30 |
| ES2172044T3 (es) | 2002-09-16 |
| JPH08500083A (ja) | 1996-01-09 |
| EP0863155B1 (en) | 2002-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69320967T2 (de) | Unterdrückung der t-zell proliferation mittels peptidfragmenten des myelin basischen protein | |
| Martin et al. | Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. | |
| EP2476436B1 (en) | Immunogenic peptides and their use in immune disorders | |
| Martin et al. | Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis | |
| US5858980A (en) | Peptide fragments of myelin basic protein | |
| Vanderlugt et al. | Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis | |
| US5614192A (en) | T cell receptor peptides as therapeutics for immune-related disease | |
| EP1105419B1 (en) | Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein | |
| DE69132863T2 (de) | Verwendung eines mbp peptides zur herstellung eines medikamentes für die behandlung von multipler sclerose | |
| JPH10509172A (ja) | ヒトミエリン塩基性タンパク質のペプチドアナログを用いた多発性硬化症の処置のための方法 | |
| EP0792286B1 (en) | Peptide analogues at position 91 of human myelin basis protein for treatment of multiple scerosis | |
| AU674494B2 (en) | T cell receptor peptides as therapeutics for immune-related disease | |
| DE69508605T2 (de) | Proinsulin-peptid-verbindungen für den nachweis und die behandlung von typ-i-diabetes | |
| DE69505376T2 (de) | Alpha b crystallin zur verwendung in diagnose und therapie von autoimmunkrankheiten, besonders multipler skerose | |
| EP2945966B1 (en) | Peptide | |
| US6379670B1 (en) | Methods for treatment of multiple sclerosis using peptide analogs of human myelin basic protein | |
| JPH10506098A (ja) | 自己免疫疾患の処置のために有用なインバリアント鎖組成物 | |
| KR100304042B1 (ko) | 면역-관련 질병용 치료제로서의 ｔ 세포 수용체 펩타이드 | |
| Irion | Peptide specificity during positive selection | |
| HK1211596B (en) | Peptide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: AUTOIMMUNE, INC., PASADENA, CALIF., US |