The role of self-Ia antigens in the murine mixed lymphocyte response.

Mouse splenic macrophages (M phi) were tested for their ability to potentiate in vitro allogeneic mixed lymphocyte response (MLR) of highly purified syngeneic responder T cells against allogeneic M phi. It was shown that even extremely low numbers of M phi syngeneic to the responder T cells were able to induce significantly stronger MLR. This potentiating effect was demonstrated to be expressed via the self-Ia antigens present on the surface of syngeneic M phi. The functional involvement of self-Ia antigens was substantiated by two approaches: (a) by using monoclonal antibodies specific for I-region determinants of the responder haplotype M phi and (b) by setting up MLR cultures with stimulator M phi of (responder X stimulator) F1 origin which express both self- and allo-Ia antigens. The results obtained in this study demonstrate that the presentation of self-Ia antigens, in conjunction with the recognition of allo-major histocompatibility complex antigens, are required for in vitro primary MLR.