Virus-specific T-cell-mediated cytotoxicity across the H–2 barrier to virus-altered alloantigen

Abstract

ALTHOUGH the biological function of the structures coded in the major murine histocompatibility (H–2) gene complex is poorly understood, some of these structures are crucially involved in most, if not all, cell-mediated immune functions^1,2. To express their immunological function, thymus-derived lymphocytes (T cells) from conventional mice and the cells with which they interact must share part of the H–2 gene complex. T helper cells and bone marrow-derived lymphocytes (B cells) usually must be compatible for the I region of H–2 (ref. 3) to act cooperatively in T-cell dependent antibody responses. This region codes for Ia cell surface antigens and immune response (Ir) genes. Also, delayed type hypersensitivity to fowl γ-globulin can be transferred adoptively to intact mice only within I-region compatible donor–recipient combinations⁴. Distinct from these models, virus-immune T cells lyse virus-infected target cells in vitro only when both are compatible at the K and/or D regions of H–2 (refs 5–7). I-region compatibility is neither necessary nor sufficient on its own. Also T-cell-mediated lysis of chemically modified targets⁸ and cytotoxicity against cells expressing either the minor histocompatibility antigens⁹ or the male Y antigen¹⁰ are similarly restricted.