Alloantigenic determinants causing secondary lymphoproliferative responses of primed T cells were investigated by blocking stimulation with monoclonal antibodies TU22, 34, 35, 36, 37, 39, 43, and 58 binding differentially to HLA-DR and SB or MB associated molecules. In particular, the use of cloned and functionally defined T cell responders greatly facilitated the assignment of stimulator-level inhibition caused by these antibodies. Thus, a novel way of functional "mapping" for stimulatory epitopes for sets of clones with restimulation specificities associated with HLA-D, SB, MB, or hitherto unidentified class II determinants is presented here. This considerably helps to elucidate the distinct immunoregulatory roles of the three major class II alloantigen systems thus far defined.