Abstract
In order to elucidate the biological role of minor lymphocyte stimulating (Mls) gene products, we have been investigating the fundamental immunogenetic characteristics of the Mls system. In this report, describe the distribution of stimulatory Mls products, Mlsa and Mlsc, in a panel of laboratory inbred strains based on the response pattern of H-2-compatible naive T-cell populations as well as monospecific Mlsa- or Mlsc-reactive T-cell clones. In addition, the expression of four different T-cell receptor (Tcr) b-V segment Tcrb-V3, −V6, −V8.1, and −V9, which were recently reported to be associated with T-cell recognition of Mls gene products in these strains, was examined. The results indicate that the majority of commonly used laboratory strains including those originally typed as Mls aare also expressing Mlsc determinants and that very few independent inbred strains are non-Mls c. Moreover, the pattern of Tcrb-V expression in spleen as well as in thymus suggests that the association between Mls expression and clonal deletion of self Mls-reactive T cells appears to be the general rule in inbred strains. Based on these results, implications for the nondetectable Mls-like gene products in other species besides the mouse are discussed.
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References
Abe, R. and Hodes, R. J.: The expression of Mls cdeterminants on Mls a, Mls b, and Mls xprototypic strains. Immunogenetics 28: 221–232, 1988a
Abe, R. and Hodes, R. J.: T cell recognition of Mlsc. I. Influence of MHC-gene products in Mlsc-specific T cell recognition. J Immunol 140: 4132–4138, 1988b
Abe, R., Ryan, J. J., and Hodes, R. J.: Mls is not a single gene, allelic system: different stimulatory Mls determinants are the products of at least two nonallelic, unlinked genes. J Exp Med 166: 1150–1155, 1987a
Abe, R., Ryan, J. J., Finkelman, F. D., and Hodes, R. J.: T cell recognition of Mls: T cell clones demonstrate polymorphism between Mlsa, Mlsc and Mlsd. J Immunol 138: 373–379, 1987b
Abe, R., Ryan, J. J., and Hodes, R. J.: Clonal analysis of the Mls system. A reappraisal of polymorphism and allelism among Mlsa, Mlsc, and Mlsd. J Exp Med 165: 1113–1129, 1987c
Abe, R., Vacchio, M. S., Fox, B., and Hodes, R. J.: Preferential expression of the T-cell receptor Vβ3 gene by Mlsc reactive T cells. Nature 335: 827–830, 1988
Abe, R., Foo-Phillips, M., and Hodes, R. J.: Analysis of Mlsc genetics. A novel instance of genetic redundancy. J Exp Med 170: 1059–1073, 1989
Abromson-Leeman, S. R., Laning, J. C., and Dorf, M. E.: T cell recognition of Mlsc,x determinants. J Immunol 140: 1726–1732, 1988
Behlke, M. A., Chou, H. S., Huppi, K., and Loh, D. Y.: Murine T-cell receptor mutants with deletons of β chain variable region genes. Proc Natl Acad Sci USA 83: 767–771, 1986
Berg, L. J., Fazekas de St. Groth, B., Pullen, A. M., and Davis, M. M.: Phenotypic differences between αβ versus β T-cell receptor transgenic mice undergoing negative selection. Nature 340: 559–561, 1989
Choi, Y., Yongwon, Kotzin, B., Herron, L., Callahan, J., Marrack, P., and Kappler, J.: Interaction of Staphylococcus aureus toxin “superantigens” with human T cells. Proc Natl Acad Sci USA 86: 8941–8945, 1989
Click, R. E. and Adelman, A.: Multigene control of Mls c. Immunogenetics 28: 412–416, 1988
Click, R. E., Adelman, A. M., and Azar, M. M.: Immune response in vitro. XIII. MLR detectability of Mlsa, Mlsb, Mlsc and Mlsd encoded products. J Immunol 134: 2948–2952, 1985
Click, R. E., Cahill, G., Schneider, D., Adelmann, A., Azar, M. M., Tarquinio, J. J., and Peck, A. B.: Nonresponsiveness to Mlsd in F1 hybrid mice carrying Mlsa and Mlsc genes. J Immunol 139: 321–325, 1987
Festenstein, H.: Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant Rev 15: 62–88, 1973
Festenstein, H.: Pertinent features of M locus determinants including revised nomenclature and strain distribution. Transplantation 18: 555–557, 1974
Festenstein, H., Bishop, C., and Taylor, B. A.: Location of Mls locus on mouse chromosome 1. Immunogenetics 5: 357–361, 1977
Finkelman, F. D., Kessler, S. W., Mushinski, J. F., and Potter, M.: IgD-secreting murine plasmacytomas. Identification and potential characterization of two IgD myeloma proteins. J Immunol 126: 680–687, 1981
Fry, A. M. and Matis, L. A.: Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature 335: 830–832, 1988
Happ, M. P., Woodland, D. L., and Palmer, E.: A third T-cell receptor β-chain variable region gene encodes reactivity to Mls-1aa gene products. Proc Natl Acad Sci USA 86: 6293–6296, 1989
Haskins, K., Hannum, C., White, J., Roehm, N., Kubo, R., Kappler, J., and Marrack, P.: The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J Exp Med 160: 452–471, 1984
Hengartner, H., Odermatt, B., Schneider, R., Schreyer, M., Walle, G., MacDonald, H. R., and Zinkernagel, R. M.: Deletion of self-reactive T cells before entry into the thymus medulla. Nature 336: 388–390, 1988
Janeway, C. A., Jr. and Katz, M. E.: The immunobiology of the T cell response to Mls-locus-disparate stimulator cells. I. Unidirectionality, new strain combinations, and the role of Ia antigens. J Immunol 134: 2057–2063, 1985
Janeway, C. A., Jr., Yagi, J., Conrad, P. J., Katz, M. E., Jones, B., Vroegop, S., and Buxser, S.: T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev 107: 61–88, 1989
Kanagawa, O., Palmer, E., and Bill, J.: The T cell receptor Vβ6 domain imparts reactivity to the Mls-1a antigen. Cell Immunol 119: 412–426, 1989
Kappler, J. W., Wade, T., White, J., Kushnir, W., Blackman, M., Bill, J., Roehm, N., and Marrack, P.: A T cell receptor Vβ segment that imparts reactivity to a class II major histocompatibility complex product. Cell 49: 263–271, 1987
Kappler, J. W., Staerz, U., White, J., and Marrack, P. C.: T cell receptor Vβ elements which recognize Mls-modified products of the major histocompatibility complex. Nature 332: 35–45, 1988
Klein, J.: Biology of the Mouse Histocompatibility-2 Complex, Springer, New York, 1975
Leo, O., Foo, M., Sachs, D. H., Samelson, L. E., and Bluestone, J. A.: Identification of a monoclonal antibody specific for murine CD3 polypeptide. Proc Natl Acad Sci USA 84: 1374–1378, 1987
MacDonald, J. R., Schneider, R., Lees, R. K., Howe, R. C., Acha-Orba, H., Festenstein, H., Zinkernagel, R. M., and Hengartner, H.: T-cell receptor Vβ use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature 332: 40–45, 1988a
MacDonald, R. B., Pedrazzini, T., Schneider, R., Louis, J. A., Zinkernagel, R. M., and Hengartner, H.: Intrathymic elimination of Mlsa-reactive (Vβ6+) cells during neonatal tolerance induction to Mlsa-encoded antigens. J Exp Med 167: 2005–2010, 1988b
Macphail, S. and Stutman, O.: H-2-linked genes determine the level of the primary in vitro anti-Mls response. Immunogenetics 24: 139–145, 1986
Marrack, P., and Kappler, J. W.: The T-cell repertoire for antigen and MHC. Immunol Today 9: 308–315, 1988
Peck, A. B., Janeway, C. A., and Wigzel, H.: T lymphocyte responses to Mls locus antigens involve recognition of H-2 I region products. Nature 266: 840–842, 1977
Pullen, A. M., Marrack, P., and Kappler, J. W.: The T cell repertoire is heavily influenced by tolerance to polymorphic self antigens. Nature 355: 796–801, 1988
Pullen, A. M., Marrack, P., and Kappler, J. W.: Evidence that Mls-2 antigens which delete Vβ3+ T cells are controlled by multiple genes. J Immunol 142: 3033–3037, 1989
Roehm, M., Herron, L., Cambier, J., DiGuisto, D., Haskins, K., Kappler, J., and Marrack, P.: The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells. Cell 38: 577–584, 1984
Ryan, J. J., Mond, J. J., Finkelman, F. D., and Scher, I.: Enhancement of the mixed lymphocyte reaction by in vivo treatment of stimulator spleen cells with anti-IgD antibody. J Immunol 130: 2534–2541, 1983
Ryan, J. J., Mond, J. J., and Finkelman, F. D.: The Mlsd-defined primary mixed lymphocyte reaction: a composite response to Mlsa and Mlsc determinants. J Immunol 138: 4385–4092, 1987a
Ryan, J. J., Miner, D. W., Mond, J. J., Finkelman, F. D., and Woody, J. N.: Regulation of the in vitro presentation of minor lymphocyte stimulating determinants by major histocompatibility complex-encoded immune response genes. J Immunol 138: 2392–2401, 1987b
Ryan, J. J., Mond, J. J., and Finkelman, F. D.: Genetic analysis of the presentation of minor lymphocyte stimulating determinants. I. Combined importance of MHC and non-MHC influences. J Immunol 141: 1063–1073, 1988
Ryan, J. J., LeJeune, B. H., Mond, J. J., and Finkerman, R. D.: Genetic analsis of the presentation of minor lymphocyte stimulating determinants. II. Differing non-MHC control of super-stimulatory and more poorly stimulatory Mls phneotypes. J Immunol 144: 2506–2517, 1990
Vacchio, M. S., and Hodes, R. J.: Selective decreases in T cell receptor Vβ expression. Decreased expression of specific Vβ families is associated with expression of multiple MHC and non-MHC gene products. J Exp Med 170: 1335–1346, 1989
White, J., Herman, A., Pullen, A. M., Kubo, R., Kappler, J., and Marrack, P.: The Vβ-specific superantigen Staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56: 27–35, 1989
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Abe, R., Foo-Phillips, M. & Hodes, R.J. Genetic analysis of the Mls system. Formal Mls typing of the commonly used inbred strains. Immunogenetics 33, 62–73 (1991). https://doi.org/10.1007/BF00211697
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DOI: https://doi.org/10.1007/BF00211697