T lymphocyte clones (TLCs) specific for Chlamydia trachomatis were obtained after limiting dilution of activated T cells from a single donor, BS (HLA-A3; B7,15; DR1, 4; DRw53; DPw4). Most of the proliferative TLCs obtained apparently used restriction elements on DR1 or DR4 molecules, expressed in the antigen-presenting cells (APC). The restriction pattern of two TLCs, however, closely followed the DRw53 specificity, while one TLC seemed to be restricted by elements on DPw4 molecules. A panel of murine monoclonal antibodies (Mabs) was employed to further dissect the restriction specificities. The proliferative capacity of some of the TLCs was studied with and without Mabs directed against different HLA molecules, using non-T cells, monocytes, and peripheral blood dendritic cells as APC. Two Mabs, 7.2 and D-54, which seem to detect monomorphic determinants on HLA-DR, inhibited both DR- and DRw53-restricted TLCs. One Mab, 109d6 which reacts with DRw53 determinants, selectively inhibited the DRw53-restricted TLCs. The DP-restricted TLC was not inhibited significantly by any tested Mabs, including two Mabs with putative specificity for monomorphic determinants on the DP molecule.