No abstract

Several surface molecules appear to be involved in antigen recognition by human T lymphocytes including the monomorphic 20/25K T3 structure present on all mature T lymphocytes and the subset-specific associative recognition elements, T4 and T8 (refs 1-8). More recently, Ti1, a clonally unique antigen recognition structure comprised of a 49,000 molecular weight (49K) alpha-chain and a 43K beta-chain, linked to T3 was identified on a major histocompatibility complex (MHC) class I specific T8+ T-cell clone, CT8III (ref. 9). To determine whether analogous receptor molecules could be found on other T-cell clones of differing specificity, we produced monoclonal antibodies against a clonal structure (Ti2) on an MHC class II specific T4+ lymphocyte, CT4II, derived from the same donor as CT8III. The Ti2 structure on CT4II is shown here to be a disulphide-linked heterodimer like Ti1 on CT8III and is composed of subunits of similar molecular weight. Monoclonal antibodies against Ti2 or Ti1 block antigen specific functions of the respective clone without showing any cross-reactivity. These findings suggest that each T lymphocyte, regardless of subset derivation or specificity, uses an analogous Ti heterodimer for antigen specific function. The latter is linked to T3 and expressed on the cell surface at an identical density (30,000-40,000 sites per cell).

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