H-2 restriction of virus-specific cytotoxicity across the H-2 barrier. Separate effector T-cell specificities are associated with self-H-2 and with the tolerated allogeneic H-2 in chimeras

Abstract

During infection with lymphocytic choriomeningitis or vaccinia virus, F1 irradiation chimeras reconstituted with bone marrow cells from or both parents generate cytotoxic T cells which can lyse targets across the H-2 barrier. However, activity of chimera T cells is H-2 restricted as shown by cold target competition experiments and selective restimulation of a secondary response in vitro; T cells of H-2k specificity which lyse tolerated infected H-2d target cells do not lyse infected H-2k or unrelated target cells and vice versa. Therefore, H-2 restriction of virus-specific cytotoxic T cells probably does not reflect need for like-like self-interactions for lysis to occur. The specificity of virus immune T cells is thus determined by the H-2K and H-2D specificities present in the infected animal and which are probably recognized unidirectionally by T cells. The results are compatible with the idea the T cells are specific for "altered alloantigen", i.e., a complex of cell surface marker and viral antigen. Alternatively, explained with a dual recognition model, T cells may possess two independently, clonally expressed receptors, a self-recognizer which is expressed for one of the syngeneic or tolerated allogeneic K or D "self" markers, and an immunologically specific receptor for viral antigen.