ionship to the T 3 Molecu la r Complex * BY STEFAN C . MEUER , : ] : KATHLEEN

Multiple lineage-specific surface molecules have recently been defined on human T lymphocytes. Although some of these appear during late intrathymic ontogeny and are maintained on all peripheral T cells (T3), others (T4, TS) arise earlier in differentiation and are selectively expressed on functional subpopulations of human T lymphocytes (1-3). In the case of the 20,000-mol wt T3 surface molecule, both its appearance in intrathymic ontogeny at the time of acquisition of immunologic competence (1, 4) and its critical role in T lymphocyte function suggested that it was closely linked to a recognition receptor for antigen. Thus, antibodies directed against T3 were able to block both the induction and the effector phase of cell-mediated lympholysis, inhibit T lymphocyte proliferative responses to soluble antigen, and be mitogenic for T lymphocytes (5-8). Anti-T4 and anti-T8 monoclonals also blocked cell-mediated lympholysis (CML) 1 (9, 10). However, whereas anti-T3 inhibited all cytolytic effector clones, anti-T4 and anti-T8 selectively abrogated killing of T4 + or T8 + cytotoxic T lymphocytes (CTL), and this inhibition occurred on the level of target cell recognition and/or binding (8, 11). Moreover, unlike T3, they did not inhibit antigen-induced proliferation. Furthermore, the correlation of T4 and T8 surface expression on CTL cells with differential recognition of class II vs. class I molecules on target cells, respectively (9, 12), implied that these T cell surface structures might be functioning in associative recognition. Given that T lymphocytes recognize antigen in a precise fashion (13-17), there must exist, in addition, discriminative surface recognition structures that are unique to individual antigen-responsive T cell clones (clonotypic). To delineate such molecules, we produced monoelonal antibodies in the present study against a human cytolytic T cell clone, CTSm (target specificity: HLA-A3), and developed a screening