Abstract
Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR alpha and beta chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the V alpha 510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat V alpha/V beta combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same V alpha/V beta combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.
Full Text
The Full Text of this article is available as a PDF (936.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
- Arden B., Klotz J. L., Siu G., Hood L. E. Diversity and structure of genes of the alpha family of mouse T-cell antigen receptor. 1985 Aug 29-Sep 4Nature. 316(6031):783–787. doi: 10.1038/316783a0. [DOI] [PubMed] [Google Scholar]
- Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
- Chou C. H., Fritz R. B., Chou F. C., Kibler R. F. The immune response of Lewis rats to peptide 68-88 of guinea pig myelin basic protein. I. T cell determinants. J Immunol. 1979 Oct;123(4):1540–1543. [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellerman K. E., Powers J. M., Brostoff S. W. A suppressor T-lymphocyte cell line for autoimmune encephalomyelitis. Nature. 1988 Jan 21;331(6153):265–267. doi: 10.1038/331265a0. [DOI] [PubMed] [Google Scholar]
- Eylar E. H., Thompson M. Allergic encephalomyelitis: the physico-chemical properities of the basic protein encephalitogen from bovine spinal cord. Arch Biochem Biophys. 1969 Feb;129(2):468–479. doi: 10.1016/0003-9861(69)90204-5. [DOI] [PubMed] [Google Scholar]
- Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
- Fritz R. B., Chou C. H., McFarlin D. E. Induction of experimental allergic encephalomyelitis in PL/J and (SJL/J x PL/J)F1 mice by myelin basic protein and its peptides: localization of a second encephalitogenic determinant. J Immunol. 1983 Jan;130(1):191–194. [PubMed] [Google Scholar]
- Happ M. P., Heber-Katz E. Differences in the repertoire of the Lewis rat T cell response to self and non-self myelin basic proteins. J Exp Med. 1988 Feb 1;167(2):502–513. doi: 10.1084/jem.167.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Happ M. P., Kiraly A. S., Offner H., Vandenbark A., Heber-Katz E. The autoreactive T cell population in experimental allergic encephalomyelitis: T cell receptor beta-chain rearrangements. J Neuroimmunol. 1988 Sep;19(3):191–204. doi: 10.1016/0165-5728(88)90002-1. [DOI] [PubMed] [Google Scholar]
- Hashim G. A. Myelin basic protein: structure, function and antigenic determinants. Immunol Rev. 1978;39:60–107. doi: 10.1111/j.1600-065x.1978.tb00397.x. [DOI] [PubMed] [Google Scholar]
- Haskins K., Hannum C., White J., Roehm N., Kubo R., Kappler J., Marrack P. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J Exp Med. 1984 Aug 1;160(2):452–471. doi: 10.1084/jem.160.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Engel I., McElligott D. L., Fink P. J., Hsu M. L., Hansburg D., Matis L. A. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science. 1988 Mar 25;239(4847):1541–1544. doi: 10.1126/science.2832942. [DOI] [PubMed] [Google Scholar]
- Hochgeschwender U., Simon H. G., Weltzien H. U., Bartels F., Becker A., Epplen J. T. Dominance of one T-cell receptor in the H-2Kb/TNP response. Nature. 1987 Mar 19;326(6110):307–309. doi: 10.1038/326307a0. [DOI] [PubMed] [Google Scholar]
- Iwamoto A., Ohashi P. S., Pircher H., Walker C. L., Michalopoulos E. E., Rupp F., Hengartner H., Mak T. W. T cell receptor variable gene usage in a specific cytotoxic T cell response. Primary structure of the antigen-MHC receptor of four hapten-specific cytotoxic T cell clones. J Exp Med. 1987 Mar 1;165(3):591–600. doi: 10.1084/jem.165.3.591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kappler J. W., Wade T., White J., Kushnir E., Blackman M., Bill J., Roehm N., Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. doi: 10.1016/0092-8674(87)90567-8. [DOI] [PubMed] [Google Scholar]
- Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
- Lider O., Reshef T., Beraud E., Ben-Nun A., Cohen I. R. Anti-idiotypic network induced by T cell vaccination against experimental autoimmune encephalomyelitis. Science. 1988 Jan 8;239(4836):181–183. doi: 10.1126/science.2447648. [DOI] [PubMed] [Google Scholar]
- Morris M., Barclay A. N., Williams A. F. Analysis of T cell receptor beta chains in rat thymus, and rat C alpha and C beta sequences. Immunogenetics. 1988;27(3):174–179. doi: 10.1007/BF00346583. [DOI] [PubMed] [Google Scholar]
- Owhashi M., Heber-Katz E. Protection from experimental allergic encephalomyelitis conferred by a monoclonal antibody directed against a shared idiotype on rat T cell receptors specific for myelin basic protein. J Exp Med. 1988 Dec 1;168(6):2153–2164. doi: 10.1084/jem.168.6.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paterson P. Y. Experimental allergic encephalomyelitis and autoimmune disease. Adv Immunol. 1966;5:131–208. doi: 10.1016/s0065-2776(08)60273-4. [DOI] [PubMed] [Google Scholar]
- Sorger S. B., Hedrick S. M., Fink P. J., Bookman M. A., Matis L. A. Generation of diversity in T cell receptor repertoire specific for pigeon cytochrome c. J Exp Med. 1987 Feb 1;165(2):279–301. doi: 10.1084/jem.165.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
- Winoto A., Urban J. L., Lan N. C., Goverman J., Hood L., Hansburg D. Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c. Nature. 1986 Dec 18;324(6098):679–682. doi: 10.1038/324679a0. [DOI] [PubMed] [Google Scholar]
- Yanagi Y., Yoshikai Y., Leggett K., Clark S. P., Aleksander I., Mak T. W. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature. 1984 Mar 8;308(5955):145–149. doi: 10.1038/308145a0. [DOI] [PubMed] [Google Scholar]
- Zamvil S. S., Mitchell D. J., Lee N. E., Moore A. C., Waldor M. K., Sakai K., Rothbard J. B., McDevitt H. O., Steinman L., Acha-Orbea H. Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis. J Exp Med. 1988 May 1;167(5):1586–1596. doi: 10.1084/jem.167.5.1586. [DOI] [PMC free article] [PubMed] [Google Scholar]