Abstract
Identity at the major histocompatibility complex (MHC) was essential for successful transfer of delayed type hypersensitivity (DTH) in mice. The regions of the MHC involved differed according to the antigen used for sensitization. In the case of fowl gamma globulin (FGG), identity atI-A was necessary, whereas with dinitrofluorobenzene (DNFB), identity at theK, I, orD region was sufficient. These different genetic constraints probably reflect differences in the mechanisms by which antigens are presented to T lymphocytes. Cells from sensitized (CBA×C57BL)F1 mice transferred DTH to FGG into parental-strain mice, but transfer was more effective in C57BL than in CBA with the same cell dose. This phenomenon is governed by the MHC, since there was better transfer intoH-2 b than intoH-2 k mice, regardless of their backgrounds. It may reflect the activity of an Ir gene-dependent process. Cells of one genotype (e.g., CBA), sensitized in chimeric mice derived from two MHC-incompatible strains (CBA↔C57BL), transferred DTH to both strains. These results do not support the notion that the genetic constraint observed in DTH transfer may be a result of the necessity for sensitized T and stimulator cells to match an identical MHC-coded cell interaction molecule. Rather, they favor the hypothesis that T cells recognize antigen, not as a naked determinant, but in close association with products of genes of the MHC.
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References
Basten, A., Miller, J.F.A.P., and Abraham, R.: Relationship between Fc receptors, antigen-binding sites on T and B cells andH-2 complex associated determinants.J. Exp. Med. 141:547–560, 1975
Bevan, M.J.: The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.J. Exp. Med. 142:1349–1364, 1975
Billingham, R.E. and Medawar, P.B.: Technique of free skin grafting in mammals.J. Exp. Biol. 28:385–402, 1951
Cantor, H. and Boyse, E.A.: Functional subclasses of T lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T cell subclasses is a differentiative process independent of antigen.J. Exp. Med. 141:1376–1389, 1975
Doherty, P.C., Blanden, R.V., and Zinkernagel, R.M.: Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity.Transplant. Rev. 29:89–124, 1976
Erb, P. and Feldmann, M.: The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens.J. Exp. Med. 142:460–472, 1975
Feldmann, M., Beverley, P.C.L., Dunkley, M., and Kontiainen, S.: Different Ly antigen phenotypes ofin vitro induced helper and suppressor cells.Nature 258:614–615, 1975
Forman, J.: On the role of theH-2 histocompatibility complex in determining the specificity of cytotoxic effector cells sensitized against syngeneic trinitrophenyl-modified targets.J. Exp. Med. 142:403–418, 1975
Gordon, R.D., Simpson, E., and Salelson, L.E.: In vitro cell-mediated immune responses to the male specific (H-Y) antigen in mice.J. Exp. Med. 142:1108–1120, 1975
Green, I., Paul, W.E., and Benacerraf, B.: A study of the passive transfer of delayed hypersensitivity to DNP-Poly-l-Lysine and DNP-GL in responder and nonresponder guinea pigs.J. Exp. Med. 126:959–967, 1967
Katz, D.H. and Benacerraf, B.: The function and interrelationships of T cell receptors,Ir genes and other histocompatibility gene products.Transplant. Rev. 22:175–195, 1975
Katz, D.H., Graves, M.G., Dorf, M.E., di Muzio, H., and Benacerraf, B.: Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in theI region of theH-2 complex.J. Exp. Med. 141:263–268, 1975
Kisielow, P., Hirst, J.A., Shiku, H., Beverley, P.C.L., Hoffmann, M.K., Boyse, E.A., and Oettgen, H.F.: Ly antigens as markers for functionally distinct subpopulations of thymus-derived lymphocytes of the mouse.Nature 253:219–220, 1975
Livnat, S., Klein, J., and Bach, F.H.: Graft versus host reaction in strains of mice identical for H-2K and H-2D antigens.Nature (New Biol.) 234:42–44, 1973
Miller, J.F.A.P., Vadas, M.A., Whitelaw, A., and Gamble, J.: A radioisotopic method to measure delayed type hypersensitivity in the mouse. II. Cell transfer studies.Int. Arch. Allergy Appl. Immunol. 49:693–708, 1975a
Miller, J.F.A.P., Vadas, M.A., Whitelaw, A., and Gamble, J.:H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice.Proc. Natl. Acad. Sci. U.S.A. 72:5095–5098, 1975b
Miller, J.F.A.P., Vadas, M.A., Whitelaw, A., and Gamble, J.: Role of major histocompatibility complex gene products in delayed type hypersensitivity.Proc. Natl. Acad. Sci. U.S.A. 73:2486–2490, 1976
Rehn, T.G., Shearer, G.M., Koren, H.S., and Inman, J.K.: Cell mediated lympholysis of N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-β-alanyl-glycylglycyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by the H-2K and H-2D serological regions of the murine major histocompatibility complex.J. Exp. Med. 143:127–142, 1976
Rosenthal, A.S. and Shevach, E.M.: Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes.J. Exp. Med. 138:1194–1212, 1973
Schrader, J.W., Cunningham, B.A., and Edelman, G.M.: Functional interactions of viral and histocompatibility antigens at tumor cell surfaces.Proc. Natl. Acad. Sci. U.S.A. 72:5066–5070, 1975
Shearer, G.M., Rehn, T.G., and Garbarino, C.A.: Cell mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components by theH-2K andH-2D serological regions of the murine major histocompatibility complex.J. Exp. Med. 141:1348–1364, 1975
Vadas, M.A., Miller, J.F.A.P., Gamble, J., and Whitelaw, A.: A radioisotopic method to measure delayed type hypersensitivity in the mouse. I. Studies in sensitized and normal mice.Int. Arch. Allergy Appl. Immunol. 49:670–692, 1975
Vadas, M.A., Miller, J.F.A.P., McKenzie, I.F.C., Chism, S.E., Shen, F.-W., Boyse, E.A., Gamble, J.R., and Whitelaw, A.M.: Ly and Ia antigen phenotypes of T cells involved in delayed type hypersensitivity and in suppression.J. Exp. Med. 144:10–19, 1976
Von Boehmer, H. and Sprent, J.: T cell function in bone marrow chimeras: absence of host-reactive T cells and cooperation of helper T cells across allogeneic barriers.Transplant. Rev. 29:3–23, 1976
Zinkernagel, R.M. and Doherty, P.C.: H-2 compatibility requirement for T cell mediated lysis of target cells injected with lymphocytic choriomeningitis virus. Different cytotoxic T cell specificities are associated with structures coded for inH-2K orH-2D.J. Exp. Med. 141:1427–1436, 1975
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Vadas, M.A., Miller, J.F.A.P., Whitelaw, A.M. et al. Regulation by the H-2 gene complex of delayed type hypersensitivity. Immunogenetics 4, 137–153 (1977). https://doi.org/10.1007/BF01575653
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DOI: https://doi.org/10.1007/BF01575653