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Fine specificity of a proliferating T-cell clone activated by a conformational determinant of the I-Ek molecule

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Abstract

We have examined the fine specificity of a stable Thy-1.2+, Lyt-1.2+, Lyt-2, and I-As− anti-I-Ek proliferating T-cell clone isolated from an A.TH anti-A.TL secondary mixed lymphocyte culture. Spleen cells from various I-Ak, Ek strains induced either a strong (A.TL, OH, and CBA) or a weak (AKR and B10.BR) proliferative response, although such cells expressed at their surface similar amounts of I-Ek antigens. Analysis of H-2 recombinant strains indicated that this clone recognized a conformational determinant carried by the E kβ E kα dimer, but not on the Ea chain per se. Among the Fl hybrid strains in which the combinatorial E kβ E kα product was detected by cellular binding with monoclonal E kβ -specific antibodies (mAb), some [(BIO.S(8R) × BlO.HTT) but not others (for example, B10.A(4R) × B10.A(5R)] were stimulatory. Seventeen anti-Ek mAb, regardless of the three spatially separated domains that they defined by antibody binding competition, completely inhibited the restimulation of this clone, whereas 15 other anti-Ak mAb failed to do so. This clone was not reactivated by stimulating cells from strains with the H-2 haplotypes p, j, v, b, r, and s but it proliferated strongly against cells from several H-2 d or H-2 q strains. Genetic evidence or blocking studies with selected mAb assigned these cross-reactive mixed lymphocyte reaction determinants to the Ad or Aq molecules, respectively. The data support the conclusion that alloreactive T cells may define a polymorphism of I-region coded products not detected by serological analyses and extend at the T-cell level the observations of serological cross-reactions between A and E molecules.

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References

  • Benacerraf, B. and Dorf, M. E.: Genetic control of specific responses and immune suppressions by Iregion genes. Cold Spring Harbor Quant. Biol. 41: 465–476, 1976

    Google Scholar 

  • Birnbaum, D. Z., Pla, M., Colombani, M., and Colombani, J.: Serological cross-reactivity between products of separate I regions. Immunogenetics 15: 71–77, 1981

    Google Scholar 

  • Cooley, M. A. and Schmitt-Verhulst, A. M.: Specific helper T cells permit differentiation of thymic antiself-trinitrophenyl cytotoxic precursor cells. J. Immunol. 123: 2328–2336, 1979

    Google Scholar 

  • David, C. S., McCormick, J. F., and Stimpfling, J. H.: Further serological and genetic characterization of the I-E and I-C subregion. In H. O. McDevitt (ed.): Ir genes and Ia antigens, pp. 9–19, Academic Press, New York, 1978

    Google Scholar 

  • Dennert, G.: Thymus derived killer cells: specificity of function and antigen recognition. Transpl. Rev. 29: 59–88, 1976

    Google Scholar 

  • Dennert, G., Swain, S. J., Waterfield, J. D., Warner, J. F., and Dutton, R. W.: Fine specificity mapping of two allospecific T cell lines: recognition of private specificities in the H-21A subregion. Eur. J. Immunol. 11: 62–64, 1981

    Google Scholar 

  • Devaux, C. and Pierres, M.: Clonal analysis of B and T cell responses to la antigens. III. Characterization of 12 xenogeneic anti-idiotypic antisera to A.TH derived anti-I-Ak and anti-I-Ek monoclonal antibodies. J. Immunol. in press, 1982

  • Elliot, B. E., Kimura, A., Peck, A. B., Nagy, Z. A., and Wigzell, H.: Receptor specificity, functional characteristics, and cell-surface phenotype of a highly selected anti-I-Ab-specific, long-term T-cell line. Immunogenetics 12: 525–540, 1981

    Google Scholar 

  • Fathman, C. G., Collavo, D., Davies, S., and Nabholz, M.: In vitro secondary MLR. I. Kinetics of proliferation and specificity of in vitro primed responder cells. J. Immunol. 118: 1232–1238, 1977

    Google Scholar 

  • Fathman, C. G. and Nabholz, M.: In vitro secondary mixed leucocyte reaction (MLR). II. Interaction MLR determinants expressed by F1 cells. Eur. J. Immunol. 7: 370–374, 1977

    Google Scholar 

  • Fathman, C. G. and Hengartner, H.: Cross-reactive mixed lymphocyte reaction determinants recognized by cloned alloreactive T cells. Proc. Natl. Acad. Sci. U.S.A. 76: 5863–5866, 1979

    Google Scholar 

  • Fathman, C. G. and Kimoto, M.: Studies utilizing murine T cell clones: Ir genes, Ia antigens and MLR stimulating determinants. Immunol. Rev. 54: 57–80, 1981

    Google Scholar 

  • Fischer-Lindahl, K. and Haussmann, B.: Expression of the I-E target antigen for T-cell killing requires two genes. Immunogenetics 11: 571–583, 1980

    Google Scholar 

  • Glasebrook, A. L. and Fitch, F. W.: Alloreactive cloned T cell lines I. Interactions between cloned amplifier and cytolytic T cell lines. J. Exp. Med. 151: 876–895, 1980

    Google Scholar 

  • Glasebrook, A. L., Sarmiento, M., Loken, M. R., Dialynas, D. P., Quintans, J., Eisenberg, L., Lutz, C. T., Wilde, D., and Fitch, F. W.: Murine T lymphocyte clones with distinct immunological functions. Immunol. Rev. 54: 225–266, 1981

    Google Scholar 

  • Guimezanes, A., Colombani, M., and Colombani, J.: Secondary mouse lymphocyte reaction (MLR) in vitro: correlation between primed cells reactivity and serological typing for la specificities. Immunogenetics 8: 127–137, 1979

    Google Scholar 

  • Jones, P. P., Murphy, D. B., and McDevitt, H. O.: Variable synthesis and expression of E. and A, (ER) la polypeptide chains in mice of different H-2 haplotypes. Immunogenetics 12: 321–337, 1981

    Google Scholar 

  • Juretic, A., Nagy, Z. A., and Klein, J.: Generation of cytotoxic T lymphocytes by the H-2-encoded E molecules. Immunogenetics 14: 73–83, 1981

    Google Scholar 

  • Klein, J., Geib, R., Chiang, C., and Hauptfeld, V.: Histocompatibility antigens controlled by the I region of the murine H-2 complex. I. Mapping of H-2A and H-2C loci. J. Exp. Med. 143: 1439–1452, 1976

    Google Scholar 

  • Klein, J., Juretic, A., Baxevanis, C. N., and Nagy, Z. A.: The traditional and a new version of the mouse H-2 complex. Nature 291: 455–460, 1981

    Google Scholar 

  • Lemke, H., Hämmerling, G. J., and Hämmerling, U.: Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/tL region in mice. Immunol. Rev. 47: 140–174, 1979

    Google Scholar 

  • McKenzie, I. F. C., Morgan, G. M., Sandrin, M. S., Michaelides, M. M., Melvold, R. W., and Kohn, H. L: B6.C-H-2 am12. A new H-2 mutation in the I region in the mouse. J. Exp. Med. 150: 1323–1338, 1979

    Google Scholar 

  • Meo, T., David, C. S., Rijnbeek, A. M., Nabholz, M., Miggiano, V. C., and Shreffler, D. C.: Inhibition of mouse MLR by anti-la sera. Transplant. Proc. VII, no 1, Suppl. 1, 127–129, 1975

    Google Scholar 

  • Ming, Y., Czitrom, A. A., and Mitchison, N. A.: Allospecific T cell lines with functional activities. Immunology, in press, 1981.

  • Mitchison, N. A.: Information transfer between the minor antigen and T cell receptor repertoire. Scand. J. Immunol., in press, 1981

  • Moller, G. (ed.): T cell clones. Immunol. Rev. 54, 1981

  • Murphy, D. B. and Shreffler, D. C.: Cross-reactivity between H-2K and H-2D products. I. Evidence for extensive and reciprocal serological cross-reactivity. J. Exp. Med. 141: 374–391, 1975

    Google Scholar 

  • Oi, V. T., Jones, P. P., Goding, J. W., Herzenberg, L. A., and Herzenberg, L. A.: Properties of monoclonal antibodies to mouse Ig allotypes, H-2 and Ia antigens. Curr. Top. in Microbiol. Immunol. 81: 115–127, 1978

    Google Scholar 

  • Ozato, K., Mayer, N., and Sachs, D. H.: Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and la antigens. J. Immunol. 124: 533–540, 1980

    Google Scholar 

  • Peck, A. B. and Wigzell, H.: The mouse primed lymphocyte typing (mPLT).I. Definition of the SD and la molecules as H-2-associated lymphocyte-stimulating (LS) determinants. Immunogenetics 6: 529–545, 1978

    Google Scholar 

  • Peck, A. B.: T-lymphocyte recognition of the I-EC gene products (la) requires concomitant recognition of I-AB gene products. Scand. J. Immunol. 11: 235–239, 1980

    Google Scholar 

  • Peck, A. B., Klein, J., and Wigzell, H.: The mouse-primed lymphocyte typing test. III. Dissociation of T lymphocyte-stimulating determinants and antibody-defined specificity of the I region-associated la antigens. J. Immunol. 125: 1078–1086, 1980

    Google Scholar 

  • Pierres, M., Ju, S. T., Waltenbaugh, C., Dorf, M. E., Benacerraf, B., and Germain, R. N.: Fine specificity of antibodies to poly(Glu60Ala30Tyr10) produced by hybrid cell lines. Proc. Natl. Acad. Sci. U.S.A. 76: 2425–2429, 1979

    Google Scholar 

  • Pierres, M., Kourilsky, F. M., Rebouah, J. P., Dosseto, M., and Caillol, D.: Distinct epitopes on Ik gene products identified by monoclonal antibodies. Eur. J. Immunol. 10: 950–957, 1980

    Google Scholar 

  • Pierres, M., Devaux, C., Dosseto, M., and Marchetto, S.: Clonal analysis of B- and T-cell responses to la antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies. Immunogenetics 14: 481–495, 1981

    Google Scholar 

  • Pierres, M., Goridis, C., and Golstein, P.: Inhibition of murine T cell mediated cytolysis and T cell proliferation by a rat monoclonal antibody imniunoprecipitating two lymphoid cell surface polypeptides of 94 000 and 180 000 molecular weight. Eur. J. Immunol., 12: 60–69, 1982

    Google Scholar 

  • Pierres, A., Schmitt-Verhulst, A. M., Devaux, C., Golstein, P., Birnbaum, D. Z., Goridis, C., and Pierres, M.: Cytolytic T cell clones against H-2I region products: an analysis using monoclonal antibodies against la, Lyt-2 and p94,180 cell surface antigens. In W. R. Clarke and P. Golstein (eds.): Mechanisms of cell-mediated cytotoxicity, Plenum, N. Y., in press, 1982

    Google Scholar 

  • Schwartz, R. H., Yano, A., Stimpfling, J. H., and Paul, W. E.: Gene complementation in the T-lymphocyte proliferative response to poly(Glu55 Lys36 Phe5)n. J. Exp. Med. 149: 40–57, 1979

    Google Scholar 

  • Schmitt-Verhulst, A. M., Golstein, P., Buferne, M., and Pierres, M.: The differential effects of distinct cytolysis-inhibiting monoclonal antibodies on growth and on cytolytic activity of T cell clones. In W. R. Clark and P. Golstein (eds.): Mechanisms of cell-mediated cytotoxicity. In press Plenum, New York, 1982

    Google Scholar 

  • Sprent, J. and Alpert, B.: Role of the H-2 complex in induction of T helper cells in vivo. II. Negative selection of discrete subgroups of T cells restricted by I-A and I-A/E determinants. J. Exp. Med. 153: 813–831, 1981

    Google Scholar 

  • Symington, F. W. and Sprent, J.: A monoclonal antibody detecting an la specificity mapping in the I-A or I-E subregion. Immunogenetics 14: 53–61, 1981

    Google Scholar 

  • Wakeland, E. K. and Klein, J.: Structural comparisons of serologically identical IA- and IE-encoded antigens from inbred and wild mice. Immunogenetics 9: 535–550, 1979

    Google Scholar 

  • Waterfield, J. D., Dennert, G., Swain, S. L., and Dutton, R. W.: Continuously proliferating allospecific T cells. 1. Specificity of cooperation with allogeneic B cell in the humoral antibody response to sheep erythrocytes. J. Exp. Med. 149: 808–814, 1979

    Google Scholar 

  • Weiss, S. and Dennert, G.: T cell lines active in the delayed-type hypersensitivity reaction (DTH). J. Immunol. 126: 2031–2035, 1981

    Google Scholar 

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Pierres, A., Pierres, M. Fine specificity of a proliferating T-cell clone activated by a conformational determinant of the I-Ek molecule. Immunogenetics 15, 399–412 (1982). https://doi.org/10.1007/BF00364263

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