Abstract
T-cell receptor (Tcr) α chains are classified into four subgroups (I, II, III, and miscellaneous) based on the amino acid residues at positions 61 and 62. Subgroup I has Gly Phe at these positions, subgroup II has Arg Phe, subgroup III has Arg Leu, and subgroup miscellaneous has several other combinations. Variability plots for subgroups I, II, and III sequences show higher values around positions 93–103, 105, 108, 111, 113, and 115, suggesting that these positions may interact with the processed antigen molecules. Smaller peaks are present at various other regions which may bind the major histocompatibility complex class I or II molecules. The patterns of variability within one subgroup are similar for all species, for human alone, and for mouse alone. These subgroup patterns appear much less complicated than patterns for sequences in all subgroups taken together, implying that subgroups may be related to Tcr functions. Among 83 mouse chains, 15 are from cytotoxic cells and 40 from helper cells. Of the 15 from cytotoxic cells, 11, 2, 0, and 2 are in subgroups I, II, III, and miscellaneous; and of the 40 from helper cells, 9, 16, 12, ans 3 are in subgroups I, II, III, and miscellaneous, respectively. Thus, a correlation between sequence and function of Tcr α chains seems possible.
Similar content being viewed by others
References
Acha-Orbea, H., Mitchell, D. J., Timmermann, L., Wraith, D. C., Tausch, G. S., Waldor, M. K., Zamvil, S. S., McDevitt, H. O., and Steinman, L.: Limited heterogeneity of T-cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54: 263–273, 1988
Amit, A. G., Mariuzza, R. A., Phillips, S. E. V., and Poljak, R. J.: Three dimensional structure of an antigen-antibody complex at 2.8 Å resolution. Science 233: 747–753, 1986
Arden, B., Klotz, J. L., Sin, G., and Hood, L. E.: Mouse T-cell antigen receptor genes: diversity and structure of genes of the α family. Nature 316: 783–787, 1985
Baer, R., Forster, A., and Rabbitts, T. H.: The mechanism of chromosome 14 inversion in a human T cell lymphoma. Cell 50: 97–105, 1987
Baer, R., Boehm, T., Yssel, H., Spits, H., and Rabbitts, T. H.: Complex rearrangement within the human Jδ-Cδ/Jα-Cα locus and aberrant recombination between Jα segments. EMBO J 7: 1661–1668, 1988
Becker, D. M., Patten, P., Chien, Y., Yokota, T., Eshhar, Z., Giedlin, M., Gascoigne, N. R. J., Goodnow, C., Wolf, R., Arai, K., and Davis, M. M.: Variability and repertoire size of T-cell receptor V αgene segments. Nature 317: 430–434, 1985
Bentley, D. L. and Rabbitts, T. H.: Human immunoglobulin variable region gene — DNA sequences of two V kgenes and a pseudogene. Nature 288: 730–733, 1980
Berman, J. E., Mellis, S. J., Pollock, R., Smith, C. L., Suh, H., Heinke, B., Kowal, C., Surti, U., Chess, L., Cantor, C. R., and Alt, F. W.: Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus. EMBO J 7: 727–738, 1988
Bougueleret, L. and Claverie, J.-M.: Variability analysis of the human and mouse T-cell receptor β chains. Immunogenetics 26: 304–308, 1987
Brodeur, P. and Riblet, R.: The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol 14: 922–930, 1984
Brodeur, R., Thompson, M. A., and Riblet, R.: The content and organization of mouse V Hgene families. In H. Cantor, L. Chess and E. Sercarz (ess.): Regulation of Immune Response, pp. 445–453, Alan R. Liss, New York, 1984
Burns, F. R., Li, X., Shen, N., Offner, H., Chou, Y. K., Vanderbark, A. A., and Heber-Katz, E.: Both rat and mouse T-cell receptors specific for the encephalitogenic determinant of mylein basic protein use similar Vα and Vβ chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. J Exp Med 169: 27–39, 1989
Capra, J. D. and Kehoe, J. M.: Variable region sequences of five immunoglobulin heavy chains of the VH III subgroup. Definitive identification of four heavy chain hypervariable regions. Proc Natl Acad Sci USA 71: 845–848, 1974
Chang, C.-H., Short, M. T., Westholm, F. A., Stevens, F. J., Wang, B.-C., Furey, W., Jr., Solomon, A., and Schiffer, M.: Novel arrangement of immunoglobulin variable domains: x-ray crystallographic analysis of the λ-chain dimer Bence-Jones protein Loc. Biochemistry 24: 4890–4897, 1985
Chien, Y., Becker, D. M., Lindsten, T., Okamura, M., Cohen, D. I., and Davis, M. M.: A third type of murine T-cell receptor gene. nature 312: 31–35, 1984
Chothia, C., Boswell, D. R., and Lesk, A. M.: The outline structure of the T-cell αβ receptor. EMBO J 7: 3745–3755, 1988
Chou, H. S., Behlke, M. A., Godambe, S. A., Russell, J. H., Brooks, C. G., and Loh, DY.: T-cell receptor genes in an alloreactive CTL clone: implications for rearrangement and germline diversity of variable gene segments. EMBO J 5: 2149–2155, 1986
Claverie, J.-M., Prochnicka-Chalufour, A., and Bougueleret, L.: Implications of a Fab-like structure for the T-cell receptor. Immunol Today 10: 10–14, 1989
Croce, C. M., Isobe, M., Palumbo, A., Puck, J., Ming, J., Tweardy, D., Erickson, J., Davis, M., and Rovera, G.: Gene for α-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science 227: 1044–1047, 1985
Davis, M. M. and Bjorkman, P. J.: T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402, 1988
Dembic, Z., Haas, W., Weiss, S., McCubrey, J., Kiefer, H., von Boehmer, H., and Steinmetz, M.: Transfer of specificity by murine α and β T-cell receptor genes. Nature 320: 232–238, 1986
Dildrop, R., A new classification of mouse VH sequences. Immunol Today 5: 84–86, 1984
Dildrop, R., Krawinkel, U., Winter, E., and Rajewsky, K.: V Hgene expression in murine lipopolysaccharide blasts distributes over the nine known V Hsubgroups and may be random. Eur J Immunol 15: 1154–1156, 1985
Fink, P. J., Matis, J. A., McElligott, D. L., Bookman, M., and Hedrick, S. M.: Correlations between T-cell specificity and the structure of the antigen receptor. Nature 321: 219–226, 1986
Happ, M. P., Kubo, R. T., Palmer, E., Born, W. K., and O'Brien, R. L.: Limited receptor repertoire in a mycobacteria-reactive subset of αδ T lymphocytes. Nature 342: 696–698, 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
Hochgeschwender, U., Simon, H.-G., Weltzien, H. U., Bartels, F., Becker, A., and Epplen, J. T.: Dominance of one T-cell receptor in the H-2Kb/TNP response. Nature 326: 307–309, 1987
Hue, I., Tracy, J., McCoy, C., Couez, D., Malissen, M.: A novel type of aberrant T-cell receptor α-chain gene rearrangement. Implications for allelic exclusion and the V-J recombination process. J Immunol 144: 4410–4419, 1990
Imai, K., Kanno, H., Shigemoto, K., Yamamoto, S., and Taniguchi, M.: Sequence and expression of transcripts of the T-cell antigen receptor α-chain gene in a functional, antigen-specific suppressor-T-cell hybridoma. Proc Natl Acad Sci USA 83: 8708–8712, 1986
Ishiguro, N., Tanaka, A., and Shinagewa, M.: Sequence analysis of bovine T-cell receptor α chain. Immunogenetics 31: 57–60, 1990
Iwamoto, A., Ohashi, P. S., Pircher, H., Walker, C. L., Michelopoulos, E. E., Rupp, F., Hengartner, H., and 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 165: 591–600, 1987
Johnson, N. A., Carland, F., Allen, P. M., and Glimcher, L. H.: T-cell receptor gene segment usage in a panel of hen-egg white lysozyme specific, I-Ak-restricted T helper hybridomas. J Immunol 142: 3298–3304, 1989
Jones, R., Alzari, P. M., and Meo, T.: Resolution of hypervariable regions in Tcr-β chains by a modified Wu-Kabat index of amino acid diversity. Proc Natl Acad Sci USA 87: 9138–9142, 1990
Kabat, E. A. and Wu, T. T.: Attempts to locate complementarity determining residues in the variable positions of light and heavy chains. Ann NY Acad Sci 190: 371–381, 1971
Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M., and Gottesman, K. S.: Sequences of Proteins of Immunological Interest, 4th Ed., US Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, MD, 1987
Kimura, N., Toyanaga, B., Yoshikei, Y., Du, R.-P., and Mak, T. W.: Sequences and repertoire of the human T cell receptor α and β chain variable region genes in thymocytes. Eur J Immunol 17: 375–383, 1987
Kishihara, K., Yoshikai, Y., Matsuzaki, G., Mak, T. W., and Nomoto, K.: Functional α and β T-cell chain receptor messages can be detected in old but not in young athymic mice. Eur J Immunol 17: 477–482, 1987
Klein, M. H., Concannon, P., Everett, M., Kim, L. D. H., Hunkapiller, T., and Hood, L.: Diversity and structure of human T-cell receptor α-chain variable region genes. Proc Natl Acad Sci USA 84: 6884–6888, 1987
Klobeck, H.-G., Bornkamm, G. W., Combriato, G., Mociket, R., Pohlenz, H.-D., and Zachau, H. G.: Subgroup IV of human immunoglobulin κ light chains is encoded by a single germline gene. Nucleic Acids Res 13: 6515–6529, 1985a
Klobeck, H.-G., Meindl, A., Combriato, G., Solomon, A., and Zachau, H. G.: Human immunoglobulin kappa light chain genes of subgroups II and III. Nucleic Acids Res 13: 6499–6513, 1985b
Kourilsky, P., Claverie, J.-M., Prochnicka-Chalufour, A., Spetz-Hagberg, A.-L, and Larsson-Sciard, E.-L.: How important is the direct recognition of polymorphic MHC residues by Tcr in the generation of the T-cell repertoire? Cold Spring Harbor Symp Quant Biol 54: 93–103, 1989
Kroemer, G., Helmberg, A., Bernot, A., Auffray, C., and Kofler, R.: Evolutionary relationship between human and mouse immunoglobulin kappa light chain variable region genes. Immunogenetics 33: 42–49, 1991
Lai, M.-Z., Huang, S.-Y., Briner, T. J., Guillet, J.-G., Smith, J. A., and Gefter, M. L.: T-cell receptor gene usage in the response to λ repressor cI protein. J Exp Med 168: 1081–1097, 1988
Leiden, J. M., Fraser, J. D., and Strominger, J. L.: The complete primary structure of the T-cell receptor genes from an alloreactive cytotoxic human human T-lymphocyte clone. Immunogenetics 24: 17–23, 1986
Luria, S., Gross, G., Horowitz, M., and Givol, D.: Promoter and enhancer elements in the rearranged α chain gene of the human T-cell receptor. EMBO J 6: 3307–3312, 1987
Malissen, M., Trucy, J., Letourneur, F., Rebai, N., Dunn, D. E., Fitch, F. W., Hood, L., and Malissen, B.: A T-cell clone expresses two T-cell receptor α genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition. Cell 55: 49–59, 1988
Marche, P. N. and Kindt, T. J.: Two distinct T-cell receptor α-chain transcripts in a rabbit T-cell line: implications for allelic exclusion in T cells. Proc Natl Acad Sci USA 83: 2190–2194, 1986
Marsh, P., Mills, F., and Gould, H.: Detection of a unique human Vκ IV germline gene by a cloned cDNA probe. Nucleic Acids Res 13: 6531–6544, 1985
McElligott, D. L., Sorger, S. B., Matis, L. A., and Hedrick, S. M.: Two distinct mechanisms account for the immune response (Ir) gene control of the T-cell response to pigeon cytochrome C. J Immunol 140: 4123–4131, 1988
Mengle-Gaw, L., Willard, H. F., Smith, C. I. E., Hammerstrom, L., Fischer, P., Sherrington, P., Lucas, G., Thompson, P. W., Baer, R., and Rabbitts, T. H.: Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J 6: 2273–2280, 1987
Milstein, C.: Linkage groups of residues in immunoglobulin chains. Nature 216: 330–332, 1967
Morris, M., Barclay, A. N., and Williams, A. F.: Analysis of T-cell receptor β chains in rat thymus, and rat Cα and Cβ sequences. Immunogenetics 27: 174–179, 1988
Okazaki, K., and Sakano, H.: Thymocyte circular DNA excised from T-cell receptor α-δ gene complex. EMBO J 7: 1669–1674, 1988
Palmer, M. S., Bentley, A., Gould, K., and Townsend, A. R. M.: The T-cell receptor from an influenza-A specific murine CTL clone. Nucleic Acids Res 17: 2353, 1989
Peck, M., Jaenichen, H.-R., Pohlenz, H.-D., Neumaier, P. S., Klobeck, H.-G., and Zachau, H. G.: Organization and evolution of a gene cluster for human immunoglobulin variable regions of the kappa type. J Mol Biol 176: 189–204, 1984
Peck, M., Smola, H., Pohlenz, H.-D., Straubinger, B., Gerl, R., and Zachau, H. G.: A large section of the gene locus encoding human immunoglobulin variable regions of the kappa type is duplicated. J Mol Biol 183: 291–299, 1985
Potter, M.: Antigen-binding myeloma proteins of mice. Adv Immunol 25: 141–211, 1977
Potter, M., Newell, J. M., Rudikoff, S., and Haber, E.: Classification of mouse Vκ groups based on partial sequence to first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol Immunol 19: 1619–1630, 1982
Rabbitts, T. H., Lefranc, M. P., Stinson, M. A., Sims, J. E., Schroder, J., Steinmetz, M., Spurr, N. L., Solomon, E., and Goodfellow, P. N.: The chromosomal location of T-cell receptor genes and a T cell rearranging gene: possible correlation with specific translocations in human T cell leukemia. EMBO J 4: 1461–1465, 1985
Rabbitts, T. H., Baer, R., Buluwela, L., Mengle-Gaw, L., Tayor, A. M., and Rabbitts, P. H.: Molecular genetics of antigen receptors and associated chromosomal abnormalities in human leukemias. Cold Spring Harbor Symp Quant Biol 51: 923–930, 1986
Raub, W. F.: The PROPHET system and resource sharing. Fed Proc 33: 2390–2392, 1974
Rupp, F., Brecher, J., Giedlin, M. A., Mosmann, T., Zimkernagel, R. M., Hengartner, H., and Joho, R. H.: T-cell antigen receptors with identical variable regions but different diversity and joining region gene segments have distinct specificaties but crossreactive idiotypes. Proc Natl Acad Sci USA 84: 219–222, 1987
Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A. C., Eisen, H. N., and Tonegawa, S.: A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature 312: 36–40, 1984
Satyanarayana, K., Hata, S., Devlin, P., Roncarolo, M. G., De Vries, J. E., Spits, H., Strominger, J. L., and Krangel, M. S.: Genomic organization of the human T-cell antigen-receptor α/δ locus. Proc Natl Acad Sci USA 85: 8166–8170, 1988
Schiffer, M., Girling, R. L., Ely, K. R., and Edmundson, A. B.: Structure of a λ-type Bence Jones protein at 3.5 Å resolution. Biochemistry 12: 4620–4631, 1973
Schiffer, M., Wu, T. T., and Kabat, E. A.: Subgroups of V-genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci USA 83: 4461–4463, 1986
Sherman, D. H., Hochman, P. S., Dick, R., Tizard, R., Ramachandran, K. L., Flavell, R. A., and Huber, B. T.: Molecular analysis of antigen recognition by insulin-specific T-cell hybridomas from B6 wild-type and bm12 mutant mice. Mol Cell Biol 7: 1865–1872, 1987
Sim, G. K., Yague, J., Nelson, J., Marrack, P., Palmer, E., Augustin, A., and Kappler, J.: Primary structure of human T-cell receptor α-chain. Nature 312: 771–775, 1984
Spinella, D. G., Hansen, T. H., Walsh, W. D., Behlke, M. A., Tillinghast, J. P., Chou, H. S., Whiteley, P. J., Kapp, J. A., Pierce, C. W., Shevach, E. M., and Loh, D. Y.: Receptor diversity of insulin-specific T-cell lines from C57BL (H-2b) mice. J Immunol 138: 3991–3995, 1987
Strominger, J. L., The γδ T-cell receptor and class Ib MHC-related proteins: enigmatic molecules of immune recognition. Cell 57: 895–898, 1989
Tan, K.-N., Datlof, B. M., Gilmore, J. A., Kronman, A. C., Lee, J. H., Maxam, A. M., and Rao, A.: The T-cell receptor Vα3 gene segment is associated with reactivity to p-azobenzenearsonate. Cell 54: 247–261, 1988
Triebel, F., Breathnach, R., Graziani, M., Hercend, T., and Debre, P.: Evidence for expression of two distinct T-cell receptor β-chain transcripts in a human diphtheria toxoid-specific T-cell clone. J Immunol 140: 300–304, 1988
Tutter, A. and Riplet, R.: Conservation of an immunoglobulin variable-region gene family indicates a specific, noncoding function. Proc Natl Acad Sci USA 86: 7460–7464, 1989
Urban, J. L., Kumar, V., Kono, D. H., Gomez, C., Horvath, S. J., Clayton, J., Ando, D. G., Sercarz, E. E., and Hood, L.: Restricted use of T-cell receptor V genes in murine autoimmune encephalomyelitis raises possibility for antibody therapy Cell 54: 577–592, 1988
Utsunomiya, Y., Bill, J., Palmer, E., Gollob, K., Takagaki, Y., and Kanagawa, O.: Analysis of a monoclonal rat antibody directed to the α-chain variable region (Vα 3) of the mouse T-cell antigen receptor. J Immunol 143: 2602–2608, 1989
Winoto, A., Mjolsness, S., and Hood, L.: Genomic organization of the genes encoding the mouse T-cell receptor α-chain: 18 J α gene segments map over 60 kilobases of DNA. Nature 361: 832–836, 1985
Winter, E., Radbruch, A., and Krawinkel, U.: Members of novel V H gene families are found in VDJ regions of polyclonally activated B-lymphocytes. EMBO J 4: 2861–2867, 1985
Wu, T. T. and Kabat, E. A.: An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med 132: 211–250, 1970
Yague, J., Blackman, M., Born, W., Marrack, P., Kappler, J., and Palmer, E.: The structure of V α and J α segments in the mouse. Nucleic Acids Res 16: 11355–11364, 1988
Yanagi, Y., Chan, A., Chin, B., Minden, M., and Mak, T. W.: Analysis of cDNA clones specific for human T cells and the α and β chains of the T-cell receptor heterodimer from a human T-cell line. Proc Natl Acad Sci USA 82: 3430–3434, 1985
Yoshikai, Y., Kimura, N., Toyonaga, B., and Mak, T. W.: Sequences and repertoire of human T-cell receptor α chain variable region genes in mature T lymphocytes. J Exp Med 164: 90–103, 1986
Author information
Authors and Affiliations
Additional information
Address correspondence and offprint requests to: M. Schiffer.
Rights and permissions
About this article
Cite this article
Schiffer, M., Kabat, E.A. & Wu, T.T. Subgroups of Tcr α chains and correlation with T-cell function. Immunogenetics 35, 224–234 (1992). https://doi.org/10.1007/BF00166827
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00166827