Abstract
The human T-cell receptor (Tcr) Vb6 family has been scrutinized for polymorphisms, both in coding as well as in intronic sequences by polymerase chain reaction (PCR), subsequent multiple electroblot hybridizations, and sequence analysis. Multiplex PCR is an efficient means of screening for Tcr variability. Four novel loci could be distinguished and several new alleles are described including two pseudogenes. The Vb6 family is characterized by an intronic stretch of simple repetitive (gt)n sequences. These elements are hypervariable, especially in the Vb6.7 subfamily, where they are particularly long. The unexpected persistence of simple repetitive sequences in Tcr and major histocompatibility complex (MHC) class II genes over extended periods of the vertebrate evolutionary history can be interpreted in parallel terms in both gene families.
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Ammer, H., Schwaiger, F. W., Kammerbauer, C., Gomolka, M., Arriens, A., Lazary, S., and Epplen, J. T.: Exonic polymorphism vs intronic simple repeat hypervariability in MHC-DRB genes. Immunogenetics 35: 332–340, 1992
Banerjee, S., Haqqi, T. M., Luthra, H. S., Stuart, J. M., and David, C. S.: Possible role of Vβ T-cell receptor genes in susceptability to collagen-induced arthritis in mice. J Exp Med 167: 832–839, 1988
Behlke, M. A., and Loh, D. Y.: Alternative splicing of murine T-cell receptor β-chain transcripts. Nature 322: 379–382, 1986
Charmley, P., Chao, A., Concannon, P., Hood, L., and Gatti, R. A.: Haplotyping the human T-cell receptor β-chain gene complex by use of restriction fragment length polymorphisms. Proc Natl Acad Sci USA 87: 4823–4827, 1990
Charmley, P., Concannon, P., and Gatti, A.: T-cell receptor β-chain DNA polymorphism frequencies in healthy HLA-DR homozygotes. Tissue Antigens 35: 157–164, 1990
Chothia, C., Boswell, D. R., and Lesk, A. M.: The outline structure of the T-cell αβ receptor. EMBO J 7: 3745–3755, 1988
Concannon, P., Gatti, R. A., and Hood, L.: Human T-cell receptor Vβ gene polymorphism. J Exp Med 165: 1130–1140, 1987
Concannon, P., Pickering, J. A., Kung, P., and Hood, L.: Diversity and structure of human T-cell receptor β-chain variable region genes. Proc Natl Acad Sci USA 83: 6598–6602, 1986
Davis, M. M. and Bjorkman, P. J.: T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402, 1988
Davis, M. M.: T-cell receptor gene diversity and selection. Annu Rev Biochem 59: 475–496, 1990
Ferradini, L., Roman-Roman, S., Azocar, J., Michalaki, H., Triebel, F., and Hercend, T.: Studies on the human T-cell receptor α/β variable region genes. II. Identification of four additional Vβ subfamilies. Eur J Immunol 21: 935–942, 1991
Groh, V., Porcelli, S., Fabbi, M., Lanier, L. L., Picker, L. J., Anderson, T., Warnke, R. A., Bhan, A. K., Strominger, J. L., and Brenner, M. B.: Human lymphocytes bearing T-cell receptor γ/δ are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med 169: 1277–1294, 1989
Hinkkanen, A. E., Steimle, V., Schlesier, M., Peter, H. H., and Epplen, J. T.: The antigen receptor of an autoreactive T-cell clone from human rheumatic synovia. Immunogenetics 29: 131–133, 1989
Ikuta, K., Ogura, T., Shimizu, A., and Honjo, T.: Low frequency of somatic mutation in β-chain variable region genes of human T-cell receptors. Proc Natl Acad Sci USA 82: 7701–7705, 1985
Jorgensen, J. L., Esser, U., Fazekas de St. Groth, B., Reay, P. A., and Davis, M. M.: Mapping T-cell receptor-peptide contrcts by variant peptide immunization of single-chain transgenics. Nature 355: 224–230, 1992
Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M., and Gottesman, K. S.: Sequences of Proteins of Immunological Interest, 4th edit., US Department of Health and Human Services, National Institutes of Health, 1987
Katz, E. H. and Acha-Orbea, H.: The V-regions disease hypothesis: evidence from autoimmune encephalomyelitis. Immunol Today 10: 164–169, 1989
Kimura, N., Toyonaga, B., Yoshikai, Y., Du, R-P., and Mak, T. W.: Sequence rand repertoire of the human T-cell receptor α and β chain variable region genes in thymocytes. Eur J Immunol 17: 375–383, 1987
Li, Y., Szabo, P., Robinson, M. A., Dang, B., and Posnett, D. N.: Allelic variations in the human T-cell receptor Vβ6.7 gene products. J Exp Med 171: 221–230, 1990
Li, Y., Szabo, P., and Posnett, D. N.: The genomic structure of human Vβ6 T-cell antigen receptor genes. J Exp Med 174: 1537–1547, 1991
Maksymowych, W. P., Gabriel, C. A., Luyrink, L., Van Kerckhove, C., Leiden, J., Choi, E., and Glass, D. N.: Polymorphic markers related to a single Tcrb-V6 gene segment. Immunogenetics 33: 281–285, 1991
Mäueler, W., Muller, M., Köhne, A. C., and Epplen, J. T.: A gel retardation assay system for studying protein binding to simple repetitive DNA sequences. Electrophoresis 13: 7–10, 1992
Miller, S. A., Dykes, D. D., and Polesky, H. F.: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215, 1988
Miyada, C. G., Klofelt, C., Reyes, A. A., McLaughlin-Taylor, E., and Wallace, R. B.: Evidence that polymorphism in the murine major histocompatibility complex may be generated by the assortment of subgene sequences. Proc Natl Acad Sci USA 82: 2890–2894, 1985
Posnett, D.: Allelic variations of human TCR V gene products. Immunol Today 11: 368–373, 1990
Rieβ, O., Kammerbauer, C., Roewer, L., Steimle, V., Andreas, A., Albert, E., Nagai, T., and Epplen, J. T.: Hypervariability of intronic simple (gt)n(ga)m repeats in HLA-DRB genes. Immunogenetics 32: 110–116, 1990
Robinson, M. A., and Kindt, T. J.: Molecular determination of T-cell receptor α and β chain genotypes in human families. Hum Immunol 14: 195–205, 1985
Robinson, M. A.: Allelic sequence variations in the hypervariable region of a T-cell receptor β chain: correlation with restriction fragment length polymorphism in human families and populations. Proc Natl Acad Sci USA 86: 9422–9426, 1989
Robinson, M. A.: The human T-cell receptor β-chain gene complex contains at least 57 variable gene segments. J Immunol 146: 4392–4397, 1991
Roman-Roman, S., Ferradini, L., Azocar, J., Genevée, C., Hercend, T., and Triebel, F.: Studies on the human T-cell receptor α/β subfamilies and 14 Jα gene segments. Eur J Immunol 21: 927–933, 1991
Rosenberg, W. M. C., Moss, P. A. H., and Bell, J. I.: Variation in human T-cell receptor Vβ and Jβ repertoire: analysis using anchor polymerase chain reaction. Eur J Immunol 22: 541–549 1991
Sambrook, J., Fritsch, E. F., and Maniatis, T.: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1989
Sarkar, G., and Sommer, S. S.: More light on PCR contamination. Nature 347: 340–341, 1990
Schiffer, M., Wu, T. T., and Kabat, E. A.: Subgroups of variable region genes of β chains of T-cell receptors for antigen. Proc Natl Acad Sci USA 83: 4461–4463, 1986
Steinman, L.: The development of rational strategies for selective immunotherap3 against autoimmune demyelating disease. Adv Immunol 49: 357–379, 1991
Toyonaga, B. and Mak, T. W.: Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol 5: 585–620, 1987
Wilson, R. K., Lai, E., Concannon, P., Barth, R. K., and Hood, L. E.: Structure, organization and polymorphism of murine and human T-cell receptor α and β chain gene families. Immunol Rev 101: 149–172, 1988
Zinkernagel, R. M. and Doherty, P. C.: Restriction of in vitro T-cell mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic of semiallogeneic system. Nature 248: 701–702, 1974
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The nucleotide sequence data reported in this paper have been submitted to the nucleotide sequence database GenBank and have been assigned the accession numbers M97503–97505.
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Gomolka, M., Epplen, C., Buitkamp, J. et al. Novel members and germline polymorphisms in the human T-cell receptor Vb6 family. Immunogenetics 37, 257–265 (1993). https://doi.org/10.1007/BF00187451
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DOI: https://doi.org/10.1007/BF00187451