Vaccinia-specific cytotoxic T-cell responses in the context of H-2 antigens not encountered in thymus may reflect aberrant recognition of a virus-H-2 complex.
BALB/c (H-2Kd-Dd) spleen and lymph node populations were specifically depleted of alloreactive potential by filtration through H-2 different, irradiated recipients. These negatively selected T cells were then stimulated with vaccinia virus in mice expressing the foreign H-2 determinants encountered previously in the filter environment. Strong virus-immune cytotoxic T-cell responses were seen in the context of H-2Kk and H-2Ks, but not 2H-2Kb. The T cells generated were not cross-reactive for the H-2Kk and H-2Kd alleles, and responsiveness was independent of concurrent presence of effector populations operating at H-2D. These findings are consisent with the idea that recognition is mediated via a complex receptor, part of which is specific for virus and part for self H-2. The capacity to interact with allogeneic, virus-infected cells may then reflect aberrant recognition of a virus-H-2-antigen complex by this single, large binding site. For instance, the T cell which would normally recognize H-2Kd-virus x, or H-2Dd-minor histocompatibility antigen Z, may now show specificity for H-2Kk-vaccinia virus. Implications for both the selective role of the thymus and for mechanisms of tolerance are discussed.
D000818:Animals; D000956:Antigens, Viral; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens