Abstract
The recognition of keyhole limpet hemocyanin by a substantial proportion of proliferating clones of murine T lymphocytes was found to be restricted by the I-E/Ck molecule, which is a combinatorial product of genes located in the I-A (Ae) and I-EIC (Eα) subregions of the murine major histocompatibility complex. The respective roles of the Ae (polymorphic) and Eα (oligomorphic) gene products in the expression of the structures which are used as restriction elements by these T-cell clones was analyzed by mating parental strains unable to present the antigen and bearing selected Ae and Eα alleles. Efficient complementation for antigen presentation was found to require the expression by accessory cells of the Aek-gene product, whereas all Eα allelic molecules were functionally equivalent. These results (a) indicate that the immunoregulatory role of I-region gene products, initially described for molecules selected for their limited number of antigenic epitopes, also applies to complex multiepitopic antigens; (b) illustrate the advantage which results from the diversity of the la molecules expressed by accessory cells for the development of potent immune responses; and (c) suggest that a correlation might exist between the degree of polymorphism of a given family of H-2 allelic molecules and their ability to be used as restriction elements for antigen recognition by T lymphocytes.
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Abbreviations
- FCS:
-
fetal calf serum
- Hepes:
-
N-2-hydroxypiperazine-N′-2 ethanesulfonic acid; in polypeptides
- G:
-
glutamate
- L:
-
lysine
- Ø:
-
phenylalanine
- KLH:
-
keyhole limpet hemocyanin
- m. Ab.:
-
monoclonal antibodies
- T cells:
-
thymus-derived cells
References
Burger, R. and Shevach, E. M.: Monoclonal antibodies to guinea pig la antigens. II. Effect on alloantigen-, antigen-, and mitogen-induced T lymphocyte proliferation in vitro. J. Exp. Med. 152: 1011–1023, 1980
Cook, R. G., Vitetta, E. S., Uhr, J. W., and Capra, J. D.: Structural studies on the murine la alloantigens. III. Tryptic peptide comparisons of allelic products of the I-E/C sub-region. Mol. Immunol. 16: 29–35, 1979
Corradin, G., Erlinger, H. M., and Chiller, J. M.: Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative responses with lymph node cells from primed mice. J. Immunol. 119: 1048–1053, 1977
Dorf, M. E. and Benacerraf, B.: Complementation of H-2-linked Ir genes in the mouse. Proc. Natl. Acad. Sci. U.S.A. 72: 3671–3675, 1975
Dubreuil, P., Pierres, M., Caillol, D., and Lemonnier, F.: Inhibition of T-cell proliferative responses by monoclonal antibodies reacting with the I-E/Ck subregion product. Immunobiol. 159: 47, 1981
Fathman, G. G. and Kimoto, M.: Studies utilizing murine T cell clones: Ir genes, la antigens and MLR stimulating determinants. Immunol. Rev. 54: 57–79, 1981
Goding, J. W.: Use of staphylococcal protein A as an immunological reagent. J. Immunol. Methods 20: 241–253, 1978
Hodes, R. J., Hatchcock, K. S., and Singer, A.: Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-A k reagent blocks helper T cell recognition of self major histocompatibility complex determinants. J. Exp. Med. 152: 1779–1794, 1980
Iványi, D. and Démant, P.: Serological characterization of previously unknown H-2 molecules identified in the products of the K d and D k regions. Immunogenetics 12: 397–408, 1981
Jones, P. P., Murphy, D. B., and McDevitt, H. O.: Two-gene control of the expression of a murine la antigen J. Exp. Med. 148: 925–939, 1978
Kimoto, M. and Fathman, G. G.: Antigen-reactive T cell clones. I. Transcomplementing hybrid I-Aregion gene products function effectively in antigen presentation. J. Exp. Med. 152: 759–770, 1980
Martinez-A. C., Coutinho, A., and Bernabé, R. R.: Hapten specific helper T cells restricted by the 1-E (C) subregion of the MHC. Immunogenetics 10: 299–303, 1980
Meo, T., David, G. S., Rijmbeck, A. M., Nabholz, M., Miggiano, V. C., and Shreffler, D. C.: Inhibition of mouse MLR by anti-Ia sera. Transplant. Proc. 7 (Suppl. 1): 127–129, 1975
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. In F. Melchers, M. Potter, N. L. Warner (eds.): Current Topics in Microbiology and Immunology, pp. 115–125, Springer-Verlag, Berlin 1978
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
Ruhl, H. and Shevach, E. M.: The effect of alloantisera on antigen-induced T cell proliferation. J. Immunol. 115: 1493–1499, 1975
Schwartz, R. H., Fathman, C. H., and Sachs, D. H.: Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant. J. Immunol. 116: 929–935, 1976a
Schwartz, R. H., David, C. S., Sachs, D. H., and Paul, W. E.: T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte proliferation with anti-Ia antisera. J. Immunol. 117: 531–540, 1976b
Schwartz, R. H., Yano, A., and Paul, W. E.: Interaction between antigen-presenting cells and primed T lymphocytes: An assessment of Ir gene expression in the antigen-presenting cells. Immunol. Rev. 40: 153–180, 1978
Schwartz, R. H., Chen, C., and Paul, W. E.: Gene complementation in the T lymphocyte proliferative response to poly (G1u56Lys35Phe9)m. Functional evidence for a restriction element coded for by both the I-A and I-E subregions. Eur. J. Immunol. 10: 708–714, 1980
Silver, J.: Trans gene complementation of I-E subregion antigens. J. Immunol. 123: 1423–1425, 1979
Sredni, B., Tse, H. Y., and Schwartz, R. H.: Direct cloning and extended culture of antigen-specific MHC-restricted, proliferating T lymphocytes. Nature 283: 581–583, 1980
Sredni, B., Matis, L. A., Lerner, E. A., Paul, W. E., and Schwartz, R. H.: Antigen-specific T cell clones restricted to unique F1 major histocompatibility complex determinants. Inhibition of proliferation with a monoclonal anti-Ia antibody. J. Exp. Med. 153: 677–693, 1981
Uhr, J. W., Capra, J. D., Vitetta, E. S., and Cook, R. G.: Organization of the immune response genes. Both subunits of murine I-A and I-E/C molecules are encoded within the I region. Science 206: 292–297, 1979
Vaz, N. M., Phillips-Quagliata, J. M., Lavine, B. B., and Vaz, E. M.: H-2-linked genetic control of immune responsiveness to ovalbumin and ovomucoid. J. Exp. Med. 134: 1335–1348, 1971
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Dubreuil, P.C., Caillol, D.H. & Lemonnier, F.A. KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes. Immunogenetics 14, 469–479 (1981). https://doi.org/10.1007/BF00350119
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DOI: https://doi.org/10.1007/BF00350119