In a radiation chimaera, host H–2 antigens determine immune responsiveness of donor cytotoxic cells

CELL membrane structures controlled by genes in the major histocompatibility complex (H–2 in mice) are involved in most immune interactions between T lymphocytes and other cells1. Cytotoxic T lymphocytes (CTL) immunised against viruses2, haptens3, minor histocompatibility antigens4 or tumour antigens5, are specific for self H–2 antigens as well as for the foreign antigen. But CTL are not restricted to recognising antigens in combination with only self H–2. H–2d homozygous CTL which have matured in an irradiated H–2d/H–2k host can respond to antigen plus H–2k in addition to antigen plus H–2d (refs 6–8). It is not known whether the H–2 environment in which T cells mature influences their range of specificity, that is, whether CTL from a normal mouse can respond quantitatively as well to antigen plus foreign H–2 as they do to antigen plus self H–2. These experiments were designed to test this influence. The results suggest that host H–2 antigens do exert an effect on the specificity of T-cell responses.