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. 1995 Feb;95(2):531–541. doi: 10.1172/JCI117695

Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibody-inducing T cells in human lupus.

A Desai-Mehta 1, C Mao 1, S Rajagopalan 1, T Robinson 1, S K Datta 1
PMCID: PMC295507  PMID: 7860735

Abstract

The production of potentially pathogenic anti-DNA autoantibodies in SLE is driven by special, autoimmune T helper (Th) cells. Herein, we sequenced the T cell receptor (TCR) alpha and beta chain genes expressed by 42 autoimmune Th lines from lupus patients that were mostly CD4+ and represented the strongest inducers of such autoantibodies. These autoimmune TCRs displayed a recurrent motif of highly charged residues in their CDR3 loops that were contributed by N-nucleotide additions and also positioned there by the recombination process. Furthermore, Th lines from four of the five patients showed a marked increase in the usage of the V alpha 8 gene family. Several independent Th lines expressed identical TCR alpha and/or beta chain sequences indicating again antigenic selection. 10 of these Th lines could be tested further for antigenic specificity. 4 of the 10 pathogenic anti-DNA autoantibody-inducing Th lines responded to the non-histone chromosomal protein HMG and two responded to nucleosomal histone proteins; all presented by HLA-DR molecules. Another Th line responded to purified DNA more than nucleosomes. Thus, these autoimmune Th cells of lupus patients respond to charged epitopes in various DNA-binding nucleoproteins that are probably processed and presented by the anti-DNA B cells they selectively help.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams S., Leblanc P., Datta S. K. Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11271–11275. doi: 10.1073/pnas.88.24.11271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ando D. G., Sercarz E. E., Hahn B. H. Mechanisms of T and B cell collaboration in the in vitro production of anti-DNA antibodies in the NZB/NZW F1 murine SLE model. J Immunol. 1987 May 15;138(10):3185–3190. [PubMed] [Google Scholar]
  3. Bianchi M. E. Production of functional rat HMG1 protein in Escherichia coli. Gene. 1991 Aug 15;104(2):271–275. doi: 10.1016/0378-1119(91)90261-9. [DOI] [PubMed] [Google Scholar]
  4. Bloom D. D., St Clair E. W., Pisetsky D. S., Clarke S. H. The anti-La response of a single MRL/Mp-lpr/lpr mouse: specificity for DNA and VH gene usage. Eur J Immunol. 1994 Jun;24(6):1332–1338. doi: 10.1002/eji.1830240614. [DOI] [PubMed] [Google Scholar]
  5. Brendel V., Dohlman J., Blaisdell B. E., Karlin S. Very long charge runs in systemic lupus erythematosus-associated autoantigens. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1536–1540. doi: 10.1073/pnas.88.4.1536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Broeren C. P., Verjans G. M., Van Eden W., Kusters J. G., Lenstra J. A., Logtenberg T. Conserved nucleotide sequences at the 5' end of T cell receptor variable genes facilitate polymerase chain reaction amplification. Eur J Immunol. 1991 Mar;21(3):569–575. doi: 10.1002/eji.1830210306. [DOI] [PubMed] [Google Scholar]
  7. Burlingame R. W., Rubin R. L., Balderas R. S., Theofilopoulos A. N. Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J Clin Invest. 1993 Apr;91(4):1687–1696. doi: 10.1172/JCI116378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bustin M., Reisch J., Einck L., Klippel J. H. Autoantibodies to nucleosomal proteins: antibodies to HMG-17 in autoimmune diseases. Science. 1982 Mar 5;215(4537):1245–1247. doi: 10.1126/science.6460317. [DOI] [PubMed] [Google Scholar]
  9. Carson D. A. The specificity of anti-DNA antibodies in systemic lupus erythematosus. J Immunol. 1991 Jan 1;146(1):1–2. [PubMed] [Google Scholar]
  10. Casciola-Rosen L. A., Anhalt G., Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994 Apr 1;179(4):1317–1330. doi: 10.1084/jem.179.4.1317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Concannon P., Pickering L. A., Kung P., Hood L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6598–6602. doi: 10.1073/pnas.83.17.6598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Constant P., Davodeau F., Peyrat M. A., Poquet Y., Puzo G., Bonneville M., Fournié J. J. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994 Apr 8;264(5156):267–270. doi: 10.1126/science.8146660. [DOI] [PubMed] [Google Scholar]
  14. Crow M. K., DelGiudice-Asch G., Zehetbauer J. B., Lawson J. L., Brot N., Weissbach H., Elkon K. B. Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus. J Clin Invest. 1994 Jul;94(1):345–352. doi: 10.1172/JCI117328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Danska J. S., Livingstone A. M., Paragas V., Ishihara T., Fathman C. G. The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides. J Exp Med. 1990 Jul 1;172(1):27–33. doi: 10.1084/jem.172.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Datta S. K., Patel H., Berry D. Induction of a cationic shift in IgG anti-DNA autoantibodies. Role of T helper cells with classical and novel phenotypes in three murine models of lupus nephritis. J Exp Med. 1987 May 1;165(5):1252–1268. doi: 10.1084/jem.165.5.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Desai D. D., Krishnan M. R., Swindle J. T., Marion T. N. Antigen-specific induction of antibodies against native mammalian DNA in nonautoimmune mice. J Immunol. 1993 Aug 1;151(3):1614–1626. [PubMed] [Google Scholar]
  18. Diamond B., Katz J. B., Paul E., Aranow C., Lustgarten D., Scharff M. D. The role of somatic mutation in the pathogenic anti-DNA response. Annu Rev Immunol. 1992;10:731–757. doi: 10.1146/annurev.iy.10.040192.003503. [DOI] [PubMed] [Google Scholar]
  19. Ebling F., Hahn B. H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates. Arthritis Rheum. 1980 Apr;23(4):392–403. doi: 10.1002/art.1780230402. [DOI] [PubMed] [Google Scholar]
  20. Ferradini L., Roman-Roman S., Azocar J., Michalaki H., Triebel F., Hercend T. Studies on the human T cell receptor alpha/beta variable region genes. II. Identification of four additional V beta subfamilies. Eur J Immunol. 1991 Apr;21(4):935–942. doi: 10.1002/eji.1830210412. [DOI] [PubMed] [Google Scholar]
  21. Fournié G. J., Lulé J., Dueymes J. M., Laval F., Delobbe I., Vernier I., Pourrat J. P. Plasma DNA in patients undergoing hemodialysis or hemofiltration: cytolysis in artificial kidney is responsible for the release of DNA in circulation. Am J Nephrol. 1989;9(5):384–391. doi: 10.1159/000168000. [DOI] [PubMed] [Google Scholar]
  22. Fredriksen K., Osei A., Sundsfjord A., Traavik T., Rekvig O. P. On the biological origin of anti-double-stranded (ds) DNA antibodies: systemic lupus erythematosus-related anti-dsDNA antibodies are induced by polyomavirus BK in lupus-prone (NZBxNZW) F1 hybrids, but not in normal mice. Eur J Immunol. 1994 Jan;24(1):66–70. doi: 10.1002/eji.1830240111. [DOI] [PubMed] [Google Scholar]
  23. Ganju R. K., Smiley S. T., Bajorath J., Novotny J., Reinherz E. L. Similarity between fluorescein-specific T-cell receptor and antibody in chemical details of antigen recognition. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11552–11556. doi: 10.1073/pnas.89.23.11552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gauthier V. J., Mannik M. A small proportion of cationic antibodies in immune complexes is sufficient to mediate their deposition in glomeruli. J Immunol. 1990 Nov 15;145(10):3348–3352. [PubMed] [Google Scholar]
  25. Gavalchin J., Datta S. K. The NZB X SWR model of lupus nephritis. II. Autoantibodies deposited in renal lesions show a distinctive and restricted idiotypic diversity. J Immunol. 1987 Jan 1;138(1):138–148. [PubMed] [Google Scholar]
  26. Goodwin G. H., Rabbani A., Nicolas P. H., Johns E. W. The isolation of the high mobility group non-histone chromosomal protein HMG 14. FEBS Lett. 1977 Aug 15;80(2):413–416. doi: 10.1016/0014-5793(77)80488-2. [DOI] [PubMed] [Google Scholar]
  27. Harley J. B., Sestak A. L., Willis L. G., Fu S. M., Hansen J. A., Reichlin M. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 1989 Jul;32(7):826–836. [PubMed] [Google Scholar]
  28. Hoffman R. W., Takeda Y., Sharp G. C., Lee D. R., Hill D. L., Kaneoka H., Caldwell C. W. Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. J Immunol. 1993 Dec 1;151(11):6460–6469. [PubMed] [Google Scholar]
  29. Jacob L., Viard J. P., Allenet B., Anin M. F., Slama F. B., Vandekerckhove J., Primo J., Markovits J., Jacob F., Bach J. F. A monoclonal anti-double-stranded DNA autoantibody binds to a 94-kDa cell-surface protein on various cell types via nucleosomes or a DNA-histone complex. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4669–4673. doi: 10.1073/pnas.86.12.4669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jaulin C., Casanova J. L., Romero P., Luescher I., Cordey A. S., Maryanski J. L., Kourilsky P. Highly diverse T cell recognition of a single Plasmodium berghei peptide presented by a series of mutant H-2Kd molecules. J Immunol. 1992 Dec 15;149(12):3990–3994. [PubMed] [Google Scholar]
  31. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  32. Kanai Y., Takeda O., Kanai Y., Miura K., Kurosawa Y. Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a study on MRL/n mice. Immunol Lett. 1993 Dec;39(1):83–89. doi: 10.1016/0165-2478(93)90168-2. [DOI] [PubMed] [Google Scholar]
  33. Kasibhatla S., Nalefski E. A., Rao A. Simultaneous involvement of all six predicted antigen binding loops of the T cell receptor in recognition of the MHC/antigenic peptide complex. J Immunol. 1993 Sep 15;151(6):3140–3151. [PubMed] [Google Scholar]
  34. Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
  35. Klein M. H., Concannon P., Everett M., Kim L. D., Hunkapiller T., Hood L. Diversity and structure of human T-cell receptor alpha-chain variable region genes. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6884–6888. doi: 10.1073/pnas.84.19.6884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lake P., Mitchison N. A. Regulatory mechanisms in the immune response to cell-surface antigens. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):589–595. doi: 10.1101/sqb.1977.041.01.068. [DOI] [PubMed] [Google Scholar]
  37. Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
  38. Lilley D. M. DNA--protein interactions. HMG has DNA wrapped up. Nature. 1992 May 28;357(6376):282–283. doi: 10.1038/357282a0. [DOI] [PubMed] [Google Scholar]
  39. Lin R. H., Mamula M. J., Hardin J. A., Janeway C. A., Jr Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991 Jun 1;173(6):1433–1439. doi: 10.1084/jem.173.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Linker-Israeli M., Quismorio F. P., Jr, Horwitz D. A. CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather than suppress, spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis. Arthritis Rheum. 1990 Aug;33(8):1216–1225. doi: 10.1002/art.1780330823. [DOI] [PubMed] [Google Scholar]
  41. Malissen M., Trucy J., Jouvin-Marche E., Cazenave P. A., Scollay R., Malissen B. Regulation of TCR alpha and beta gene allelic exclusion during T-cell development. Immunol Today. 1992 Aug;13(8):315–322. doi: 10.1016/0167-5699(92)90044-8. [DOI] [PubMed] [Google Scholar]
  42. Mamula M. J., Fatenejad S., Craft J. B cells process and present lupus autoantigens that initiate autoimmune T cell responses. J Immunol. 1994 Feb 1;152(3):1453–1461. [PubMed] [Google Scholar]
  43. Mao C., Osman G. E., Adams S., Datta S. K. T cell receptor alpha-chain repertoire of pathogenic autoantibody-inducing T cells in lupus mice. J Immunol. 1994 Feb 1;152(3):1462–1470. [PubMed] [Google Scholar]
  44. Martin R., Howell M. D., Jaraquemada D., Flerlage M., Richert J., Brostoff S., Long E. O., McFarlin D. E., McFarland H. F. A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis. J Exp Med. 1991 Jan 1;173(1):19–24. doi: 10.1084/jem.173.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Mohan C., Adams S., Stanik V., Datta S. K. Nucleosome: a major immunogen for pathogenic autoantibody-inducing T cells of lupus. J Exp Med. 1993 May 1;177(5):1367–1381. doi: 10.1084/jem.177.5.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Moss P. A., Rosenberg W. M., Bell J. I. The human T cell receptor in health and disease. Annu Rev Immunol. 1992;10:71–96. doi: 10.1146/annurev.iy.10.040192.000443. [DOI] [PubMed] [Google Scholar]
  47. Naiki M., Chiang B. L., Cawley D., Ansari A., Rozzo S. J., Kotzin B. L., Zlotnik A., Gershwin M. E. Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. J Immunol. 1992 Dec 15;149(12):4109–4115. [PubMed] [Google Scholar]
  48. Obata F., Tsunoda M., Kaneko T., Ito K., Ito I., Masewicz S., Mickelson E. M., Ollier W. E., Pawelec G., Cella M. Human T-cell receptor TCRAV, TCRBV, and TCRAJ sequences newly found in T-cell clones reactive with allogeneic HLA class II antigens. Immunogenetics. 1993;38(1):67–70. doi: 10.1007/BF00216395. [DOI] [PubMed] [Google Scholar]
  49. Oksenberg J. R., Stuart S., Begovich A. B., Bell R. B., Erlich H. A., Steinman L., Bernard C. C. Limited heterogeneity of rearranged T-cell receptor V alpha transcripts in brains of multiple sclerosis patients. Nature. 1990 May 24;345(6273):344–346. doi: 10.1038/345344a0. [DOI] [PubMed] [Google Scholar]
  50. Pluschke G., Ricken G., Taube H., Kroninger S., Melchers I., Peter H. H., Eichmann K., Krawinkel U. Biased T cell receptor V alpha region repertoire in the synovial fluid of rheumatoid arthritis patients. Eur J Immunol. 1991 Nov;21(11):2749–2754. doi: 10.1002/eji.1830211115. [DOI] [PubMed] [Google Scholar]
  51. Portanova J. P., Arndt R. E., Kotzin B. L. Selective production of autoantibodies in graft-vs-host-induced and spontaneous murine lupus. Predominant reactivity with histone regions accessible in chromatin. J Immunol. 1988 Feb 1;140(3):755–760. [PubMed] [Google Scholar]
  52. Radic M. Z., Weigert M. Genetic and structural evidence for antigen selection of anti-DNA antibodies. Annu Rev Immunol. 1994;12:487–520. doi: 10.1146/annurev.iy.12.040194.002415. [DOI] [PubMed] [Google Scholar]
  53. Rajagopalan S., Mao C., Datta S. K. Pathogenic autoantibody-inducing gamma/delta T helper cells from patients with lupus nephritis express unusual T cell receptors. Clin Immunol Immunopathol. 1992 Mar;62(3):344–350. doi: 10.1016/0090-1229(92)90113-3. [DOI] [PubMed] [Google Scholar]
  54. Rajagopalan S., Zordan T., Tsokos G. C., Datta S. K. Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7020–7024. doi: 10.1073/pnas.87.18.7020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Reichlin M., Martin A., Taylor-Albert E., Tsuzaka K., Zhang W., Reichlin M. W., Koren E., Ebling F. M., Tsao B., Hahn B. H. Lupus autoantibodies to native DNA cross-react with the A and D SnRNP polypeptides. J Clin Invest. 1994 Jan;93(1):443–449. doi: 10.1172/JCI116980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Roman-Roman S., Ferradini L., Azocar J., Genevée C., Hercend T., Triebel F. Studies on the human T cell receptor alpha/beta variable region genes. I. Identification of 7 additional V alpha subfamilies and 14 J alpha gene segments. Eur J Immunol. 1991 Apr;21(4):927–933. doi: 10.1002/eji.1830210411. [DOI] [PubMed] [Google Scholar]
  57. Rumore P. M., Steinman C. R. Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone. J Clin Invest. 1990 Jul;86(1):69–74. doi: 10.1172/JCI114716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Sainis K., Datta S. K. CD4+ T cell lines with selective patterns of autoreactivity as well as CD4- CD8- T helper cell lines augment the production of idiotypes shared by pathogenic anti-DNA autoantibodies in the NZB x SWR model of lupus nephritis. J Immunol. 1988 Apr 1;140(7):2215–2224. [PubMed] [Google Scholar]
  59. Shivakumar S., Tsokos G. C., Datta S. K. T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. J Immunol. 1989 Jul 1;143(1):103–112. [PubMed] [Google Scholar]
  60. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  61. Sobel E. S., Kakkanaiah V. N., Kakkanaiah M., Cheek R. L., Cohen P. L., Eisenberg R. A. T-B collaboration for autoantibody production in lpr mice is cognate and MHC-restricted. J Immunol. 1994 Jun 15;152(12):6011–6016. [PubMed] [Google Scholar]
  62. Suenaga R., Abdou N. I. Cationic and high affinity serum IgG anti-dsDNA antibodies in active lupus nephritis. Clin Exp Immunol. 1993 Dec;94(3):418–422. doi: 10.1111/j.1365-2249.1993.tb08211.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Suzuki N., Harada T., Mizushima Y., Sakane T. Possible pathogenic role of cationic anti-DNA autoantibodies in the development of nephritis in patients with systemic lupus erythematosus. J Immunol. 1993 Jul 15;151(2):1128–1136. [PubMed] [Google Scholar]
  64. Termaat R. M., Brinkman K., Nossent J. C., Swaak A. J., Smeenk R. J., Berden J. H. Anti-heparan sulphate reactivity in sera from patients with systemic lupus erythematosus with renal or non-renal manifestations. Clin Exp Immunol. 1990 Nov;82(2):268–274. doi: 10.1111/j.1365-2249.1990.tb05438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624–8628. doi: 10.1073/pnas.82.24.8624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Uematsu Y., Wege H., Straus A., Ott M., Bannwarth W., Lanchbury J., Panayi G., Steinmetz M. The T-cell-receptor repertoire in the synovial fluid of a patient with rheumatoid arthritis is polyclonal. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8534–8538. doi: 10.1073/pnas.88.19.8534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Utz U., Brooks J. A., McFarland H. F., Martin R., Biddison W. E. Heterogeneity of T-cell receptor alpha-chain complementarity-determining region 3 in myelin basic protein-specific T cells increases with severity of multiple sclerosis. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5567–5571. doi: 10.1073/pnas.91.12.5567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Wucherpfennig K. W., Ota K., Endo N., Seidman J. G., Rosenzweig A., Weiner H. L., Hafler D. A. Shared human T cell receptor V beta usage to immunodominant regions of myelin basic protein. Science. 1990 May 25;248(4958):1016–1019. doi: 10.1126/science.1693015. [DOI] [PubMed] [Google Scholar]

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