The role of Ia molecules in the activation of T lymphocytes. II. Ia-restricted recognition of allo K/D antigens is required for class I MHC-stimulated mixed lymphocyte responses.

The role of Ia molecules in the T cell proliferative response to class I (H2K/D) MHC alloantigens was examined. Proliferation in response to allo-K/D antigenic stimulation, but not to allo-Ia, was markedly inhibited by the addition of monoclonal anti-responder Ia antibodies to cultures in the absence of C. This anti-Ia blocking was observed in responses against both allelic and mutant class I antigens. Partial blocking was observed by using an anti-I-A or anti-I-E monoclonal antibody alone, whereas marked inhibition was seen with these two reagents together when the proliferating cells derived from a responder strain expressing both IA and IE gene products. Syngeneic Ia molecules appear to function as restriction elements, because they are required even in the presence of a source of exogenous second signal, phorbol myristic acetate or IL 1. The K/D-specific response required a responding cell that bears both Lyt-1 and -2 antigens, whereas responses generated to alloantigenic differences, including the I region, require only an Ly-1+ cell. The implications of these data with respect to the repertoire of the alloreactive proliferating T cell and the expression of the Lyt-2 antigen by such cells are discussed.