Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex.

Abstract

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

Regulation of T cell autocrine growth. T4+ cells become refractory to interleukin 2.

“…Thus, the in vitro cell population should have reflected, as closely as possible, the cells that are likely to encounter antigen in vivo. Moreover, anti-T3 was selected as the initial activating ligand since it is now known (24,25) that antigens activate T cells via interaction with a 90 kD disulfide-linked heterodimer noncovalently associated with three smaller proteins on the cell surface, the Ti-T3 complex. By using mAb reactive specifically with T3, we hoped to activate all mature T4 + and T8 + cells and at the same time avoid stimulation of other surface structures that might affect the resulting IL-2-promoted response.…”

A brief history of CD8 T cells

“…Moreover, studies in the 1970s claiming that certain immunoglobulin isotypes were associated uniquely with T cells (IgT) proved irreproducible, confusing, and incorrect. Finally, in 1982-3, several groups generated clonotypic antibodies against various T cell hybridomas and tumors [27][28][29][30][31]. These antibodies permitted a long awaited biochemical analysis of the putative TCR, which revealed a heterodimeric receptor with both constant and variable regions, similar to the immunoglobulin molecule.…”

Human double-negative (CD4-CD8-) T cells bearing αβ T cell receptor possess both helper and cytotoxic activities

“…As shown in Table 3, all clones lysed NK-sensitive K562 eells, indieating tbat CD4-CD8-TCRa/?+ T cells bave MHC-unrestricted cytotoxic activity in addition to helper activity for immunoglobulin production by B cells. It has been shown that CD3/TCR eomplex is essential for the mediation of antigen-specific cytotoxicity in both CD4' and CD8+ cytotoxic T lymphocytes (CTL), based on the findings that CD3 or anti-TCR MoAb inhibited tbeir cytotoxicity (Landegren et at., 1982;Meuer et al, 1982;Meuer et al, 1983). Moreover, MHCunrestricted cytotoxicity mediated by both CD4+ and CD8+ CTL was found to be inhibited also by CD3 MoAb in most eases (Tbiele & Lipsky, 1989).…”