Cloned human T lymphocyte lines were generated against trinitrophenyl (TNP)-modified autologous cells from four different individuals. By examining the reactivity patterns of 58 of these T cell clones (TLC) on panels of HLA-typed antigen presenting cells and employing monoclonal antibodies (MoAb) for inhibition studies, we have demonstrated that TNP may be recognized in the context of different DR and DP associated determinants. We did not identify any TLC restricted by determinants associated uniquely with DQ. Determinants associated with the expression of DR1,2,4,5, and 7 as well as the supertypic specificities DRw52 (MT2) and DRw53 (MT3) functioned as restriction elements. In addition, at least two antigenically distinct regions of the DP4 molecule appeared to function in the presentation of TNP. One TNP-specific TLC recognized a determinant associated with the expression of DP4 while another recognized TNP in the context of a highly nonpolymorphic determinant on DP which was expressed on all stimulators tested. Monoclonal antibody blocking studies suggest that these two determinants lie on different portions of the DP molecule. These studies demonstrated that both polymorphic and relatively nonpolymorphic restriction determinants on DR and DP may function in the presentation of conventional antigen to autologous lymphocytes.