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Polymorphisms and diversity of T-cell receptor-γ proteins expressed in mouse spleen


Bulk populations of T-cell receptor (Tcr) γδ-expressing splenocytes from different inbred strains of mice were examined for the diversity of Tcr γδ proteins. Immunoprecipitations with anti-Cγ1/2, anti-Cγ4, and anti-Vγ1 sera demonstrated that splenocytes from B10.BR, C57BL/6, and C57L strains of mice expressed the same array of Tcrγ proteins, namely Vγ1-Cγ2, Vγ1-Cγ4, and Vγ2-Cγ1, although the Tcr γδ heterodimers observed for each of these strains were biochemically distinct. Examination of bulk splenic Tcr γδ heterodimers from several other inbred strains of mice demonstrated that each of the strains could be categorized into one of three basic phenotypes. For several reasons, the differences observed between the strains appeared to be solely dependent on polymorphisms of the Tcrg loci. First, F1 mice co-expressed both parental Tcr γδ phenotypes. Second, the distinguishing polymorphism between mice of phenotype 1 and phenotypes 2 or 3 was due to the presence of an N-linked glycosylation site within the Tcrg-C1 gene segment, previously described for BALB.B and C57BL/6 Tcrg-C1 genes. Finally, the Vγ1-Cγ4 polymorphism between mice of phenotype 3 and phenotypes 1 or 2 was due to differences in core protein size. Furthermore, the three defined Tcrγ chains were expressed independently of the major histocompatibility complex (MHC) haplotype. Although no striking qualitative differences in Tcr γδ heterodimers were observed between strains (including those with autoimmune disorders), a quantitative difference in the relative amount of Cγ4-encoded proteins was observed on Tcr γδ splenocytes from both newborn euthymic and adult athymic mice when compared to adult Tcr γδ splenocytes from euthymic mice. These results demonstrate that genetic polymorphisms exist among different mouse strains and suggest that selective developmental pressures may govern Tcr γδ expression.

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  1. Abe, R. and Hodes, R. J.: T-cell recognition of minor lymphocyte stimulating (Mls) gene products. Annu Rev Immunol 7: 683–708, 1989

  2. Asarnow, D. M., Kuziel, W. A., Bonyhadi, M., Tigelaar, R. E., Tucker, P. W., and Allison, J. P.: Limited diversity of gamma delta antigen receptor genes of Thy-1 + dendritic epidermal cells. Cell 55: 837–847, 1988

  3. Augustin, A., Kubo, R. T., and Sim, G.-K.: Resident pulmonary lymphocytes expressing the γ/δ T-cell receptor. Nature 340: 239–241, 1989

  4. Bluestone, J. A. and Matis, L. A.: TCR gamma delta cells — minor redundant T cell subset or specialized immune system component? J Immunol 142: 1785–1788, 1989

  5. Bluestone, J. A., Cron, R. Q., Cotterman, M., Houlden, B. A., and Matis, L. A.: Structure and specificity of T cell receptor gamma/delta on major histocompatibility complex antigen-specific CD3+, CD4−, CD8− T lymphocytes. J Exp Med 168: 1899–1916, 1988

  6. Brenner, M. B., McLean, J., Dialynas, D. P., Strominger, J. L., Smith, J. A., Owen, F. L., Seidman, J. G., Ip, S., Rosen, F., and Krangel, M. S.: Identification of a putative second T-cell receptor. Nature 322: 145–149, 1986

  7. Ceredig, R., Lowenthal, J. W., Nabholz, M., and MacDonald, H. R.: Expression of interleukin-2 receptors as a differentiation marker on intrathymic stem cells. Nature 314: 98–100, 1985

  8. Chien, Y.-H., Iwashima, M., Kaplan, K. B., Elliott, J. F., and Davis, M. M.: A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. Nature 327: 677–682, 1987

  9. Ciccone, E., Viale, O., Bottino, C., Pende, D., Migone, N., Casorati, G., Tambussi, G., Moretta, A., and Moretta, L.: Antigen recognition by human T cell receptor gamma-positive lymphocytes. Specific lysis of allogeneic cells after activation in mixed lymphocyte culture. J Exp Med 167: 1517–1522, 1988

  10. Cron, R. Q., Koning, F., Maloy, W. L., Pardoll, D., Coligan, J. E., and Bluestone, J. A.: Peripheral murine CD3+, CD4−, CD8− T lymphocytes express novel T cell receptor gamma delta structures. J Immunol 141: 1074–1082, 1988

  11. Cron, R. Q., Gajewski, T. F., Sharrow, S. O., Fitch, F. W., Matis, L. A., and Bluestone, J. A.: Phenotypic and functional analysis of murine CD3+, CD4−, CD8− TCR-gamma delta-expressing peripheral T cells. J Immunol 142: 3754–3762, 1989a

  12. Cron, R. Q., Esquerra, A., Coligan, J. E., Houlden, B. A., Bluestone, J. A., and Maloy, W. L.: Identification of distinct T cell receptor (TCR)-gamma delta heterodimers using an anti-TCR-gamma variable region serum. J Immunol 143: 3769–3775, 1989b

  13. Dembic, Z., Bannwarth, W., Taylor, B. A., and Steinmetz, M.: The gene encoding the T-cell receptor α-chain maps close to the Np-2 locus on mouse chromosome 14. Nature 314: 271–273, 1985

  14. Elliott, J. F., Rock, E. P., Patten, P. A., Davis, M. M., and Chien, Y.-H.: The Adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes. Nature 331: 627–631, 1988

  15. Garman, R. D., Doherty, P. J., and Raulet, D. H.: Diversity, rearrangement, and expression of murine T cell gamma genes. Cell 45: 733–742, 1986

  16. Goodman, T. and Lefrancois, L.: Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 333: 855–857, 1988

  17. Havran, W. L. and Allison, J. P.: Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 335: 443–445, 1988

  18. Havran, W. L., Grell, S., Duwe, G., Kimura, J., Wilson, A., Kruisbeek, A. M., O'Brien, R. L., Born, W., Tigelaar, R. E., and Allison, J. P.: Limited diversity of T-cell receptor gamma-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V gamma 3-specific monoclonal antibody. Proc Natl Acad Sci USA 86: 4185–4189, 1989

  19. Hayday, A. C., Saito, H., Gillies, S. D., Kranz, D. M., Tanigawa, G., Eisen, H. N., and Tonegawa, S.: Structure, organization, and somatic rearrangement of T cell gamma genes. Cell 40: 259–269, 1985

  20. Houlden, B. A., cron, R. Q., Coligan, J. E., and Bluestone, J. A.: Systematic development of distinct T cell receptor-gamma delta T cell subsets during fetal ontogeny. J Immunol 141: 3753–3759, 1988

  21. Itohara, S., Nakanishi, N., Kanagawa, O., Kubo, R., and Tonegawa, S.: Monoclonal antibodies specific to native murine T-cell receptor γδ: analysis of γδ T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci USA 86: 5094–5098, 1989

  22. Iwamoto, A., Rupp, F., Ohashi, P. S., Walker, C. L., Pircher, H., Joho, R., Hengartner, H., and Mak, T. W.: T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes. J Exp Med 163: 1203–1212, 1986

  23. Klotz, J. L., Barth, R. K., Kiser, G. L., Hood, L. E., and Kronenberg, M.: Restriction fragment length polymorphisms of the mouse T-cell receptor gene families. Immunogenetics 29: 191–201, 1989

  24. Koning, F., Stingl, G., Yokoyama, W. M., Yamada, H., Maloy, W. L., Tschachler, E., Shevach, E. M., and Coligan, J. E.: Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal cell lines. Science 236: 834–837, 1987

  25. Koning, F., Yokoyama, W. M., Maloy, W. L., Stingl, G., McConnell, T. J., Cohen, D. I., Shevach, E. M., and Coligan, J. E.: Expression of C gamma 4 T cell receptors and lack of isotype exclusion by dendritic epidermal T cell lines. J Immunol 141: 2057–2062, 1988

  26. Lanier, L. L. and Weiss, A.: Presence of Ti (WT31) negative T lymphocytes in normal blood and thymus. Nature 324: 268–270, 1986

  27. Leo, O., Foo, M., Sachs, D. H., Samelson, L. E., and Bluestone, J. A.: Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci USA 84: 1374–1378, 1987a

  28. Leo, O., Foo, M., Segal, D. M., Shevach, E., and Bluestone, J. A.: Activation of murine T lymphocytes with monoclonal antibodies: detection on Lyt-2+ cells of an antigen not associated with the T cell receptor complex but involved in T cell activation. J Immunol 139: 1214–1222, 1987b

  29. Lew, A. M., Pardoll, D. M., Maloy, W. L., Fowlkes, B. J., Kruisbeek, A., Cheng, S.-F., Germain, R. N., Bluestone, J. A., Schwartz, R. H., and Coligan, J. E.: Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science 234: 1401–1405, 1986

  30. Li, Y., Szabo, P., and Posnett, D. N.: Molecular genotypes of the human T cell receptor γ-chain. J Immunol 140: 1300–1303, 1988

  31. Mackay, C. R., Hein, W. R., Brown, M. H., and Matzinger, P.: Unusual expression of CD2 in sheep: implications for T cell interactions. Eur J Immunol 18: 1681–1688, 1988

  32. Maeda, K., Nakanishi, N., Rogers, B. L., Haser, W. G., Shitara, K., Yoshida, H., Takagaki, Y., Augustin, A. A., and Tonegawa, S.: Expression of the T-cell receptor gamma-chain gene products on the surface of peripheral T cells and T-cell blasts generated by allogeneic mixed lymphocyte reaction. Proc Natl Acad Sci USA 84: 6536–6540, 1987

  33. Matis, L. A., Cron, R., and Bluestone, J. A.: Major histocompatibility complex-linked specificity of γδ receptor-bearing T lymphocytes. Nature 330: 262–264, 1987

  34. Matis, L. A., Fry, A. M., Cron, R. Q., Cotterman, M. M., Dick, R. F., and Bluestone, J. A.: Structure and specificity of a class II MHC alloreactive γδ T cell receptor heterodimer. Science 245: 746–749, 1989

  35. Pardoll, D. M., Fowlkes, B. J., Bluestone, J. A., Kruisbeek, A., Maloy, W. L., Coligan, J. E., and Schwartz, R. H.: Differential expression of two distinct T-cell receptors during thymocyte development. Nature 326: 79–81, 1987

  36. Pardoll, D. M., Fowlkes, B. J., Lew, A. M., Maloy, W. L., Weston, M. A., Bluestone, J. A., Schwartz, R. H., Coligan, J. E., and Kruisbeek, A. M.: Thymus-dependent and thymus-independent developmental pathways for peripheral T cell receptor-gamma delta-bearing lymphocytes. J Immunol 140: 4091–4096, 1988

  37. Pelicci, P. G., Subar, M., Weiss, A., Dalla-Favera, R., and Littman, D. R.: Molecular diversity of the human T-gamma constant region genes. Science 237: 1051–1055, 1987

  38. Pelkonen, J., Traunecker, A., and Karjalainen, K.: A new mouse TCR V gamma gene that shows remarkable evolutionary conservation. EMBO J 6: 1941–1944, 1987

  39. Raulet, D. H.: The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol 7: 175–207, 1989

  40. Rivas, A., Koide, J., Cleary, M. L., and Engleman, E. G.: Evidence for involvement of the gamma, delta T cell antigen receptor in cytotoxicity mediated by human alloantigen-specific T cell clones. J Immunol 142: 1840–1846, 1989

  41. Saito, H., Kranz, D. M., Takagaki, Y., Hayday, A. C., Eisen, H. N., and Tonegawa, S.: Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 309: 757–762, 1984

  42. Sarmiento, M., Glasebrook, A. L., and Fitch, F. W.: IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J Immunol 125: 2665–2672, 1980

  43. Sowder, J. T., Chen, C.-L., Ager, L. L., Chan, M. M., and Cooper, M. D.: A large subpopulation of avian T cells express a homologue of the mammalian Tγ/δ receptor. J Exp Med 167: 315–322, 1988

  44. Takagaki, Y., DeCloux, A., Bonneville, M., and Tonegawa, S.: Diversity of γδ T-cell receptors on murine intestinal intraepithelial lymphocytes. Nature 339: 712–714, 1989

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Cron, R.Q., Coligan, J.E. & Bluestone, J.A. Polymorphisms and diversity of T-cell receptor-γ proteins expressed in mouse spleen. Immunogenetics 31, 220–228 (1990). https://doi.org/10.1007/BF00204891

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  • Major Histocompatibility Complex
  • Inbred Strain
  • Athymic Mouse
  • Mouse Spleen
  • Developmental Pressure