H-2 COMPLEMENTATION IN ANTI-H-Y CYTOTOXIC T-CELL RESPONSES CAN OCCUR IN CHIMERIC MICE

Cytotoxic T-cell responses against the H-Y antigen in mice are under the control of major histocompatibility complex genes. Not only must cytotoxic T cells recognize both H-Y antigens and 'self' H-2K/D molecules to lyse male target cells, but also 'appropriate association' between H-Y antigens and H-2K/D antigens is required to induce such cytotoxic responses. Furthermore, it is suggested that appropriate association with H-2-I antigens may also be required to generate H-Y specific helper cells for the cytotoxic response. BALB/c(K(d)I(d)D(d)) mice are nonresponders against syngeneic H-Y antigens, because they lack appropriate associative H-2K/D antigens. This results in the failure of generation of anti H-Y cytotoxic cells, although helper cells may be induced. F1 hybrid mice (BALB/c x C3H/He)F1 or H-2 recombinant mice C3H x OH(K(d)I(d)D(k)) are responders, because H-2D(k)-(and H-2K(k) in the F1) molecules offer appropriate association to H-Y antigens. We here report that allophenic chimeras (H-2(d)←→H-2(K)) and irradiation bone marrow chimeras [H-2(d) + H-2(k)→F1(H-2(d) x H-2(k)) generate anti-H-Y cytotoxic responses but that cells of the BALB/c(H-2(d)) genotype comprise most if not all of the cytotoxic cells. A working model is proposed to account for major histocompatibility complex control over anti-H-Y cytotoxic T-cell responses.