We have analyzed the signals influencing the generation of MHC class II alospecific CTL and have found that the development of these CTL is actively regulated in primary in vitro cultures (MLC) by Lyt2+ cells triggered in response to MHC class I alloantigens. Class II allospecific CTL can be readily generated in primary cultures, but the presence of a simultaneous class I MHC stimulus in these cultures causes a marked reduction of class II-specific CTL activation. This reduction can be prevented by adding to culture a dose of monoclonal anti-Lyt2 antibody that does not block the generation of class I-specific CTL. The role of MHC class I alloantigens in the regulation of class II allospecific responses illustrates that T cells recognizing class I and class II MHC antigens in MLC interact in a complex, and non-reciprocal, manner to influence the final effector T cell repertoire elicited by this complex immunogenic challenge.
