Required Coexpression of T 3 and the Antigen

During the past year, several laboratories have developed monoclonal antibodies reactive with idiotypic-like determinants expressed on human and murine T cell clones, lines, or hybridomas (1-5). These antibodies are felt to react with the antigen receptors of these cells. Such antibodies can mimic the effects of antigen by specifically activating the immunizing T cell, or, under appropriate circumstances, can specifically block the antigen reactivity of the immunizing T cell (2-7). Immunoprecipitates prepared from different cells with such antibodies contain distinct heterodimers of 80-90 kilodaltons (kD) under nonreducing conditions and two chains of 37-52 kD under reducing conditions (1-7). On human cells, another set of molecules, T3, has been associated with such putative T cell antigen receptors. T3 consists of at least three noncovalently linked distinct peptides, each of which has not been shown to exhibit any structural or antigenic polymorphism (8). Several observations have suggested an association between T3 and the putative antigen receptor: T3 co-modulates with antigen receptor determinants on T cell clones (2); the induction of an unresponsive state in T cell clones exposed to soluble antigen is accompanied by a diminished expression of T3 (9); T3 and receptor binding sites are stoichiometric (10); immunoprecipitates of T3, under some conditions, contain the T cell receptor heterodimer in addition to the peptides representing T3 (11); and the appearance of T3 during T cell ontogeny has been linked to the expression of antigen receptor-like molecules on T cells (12). Despite these observations, however, the role of T3 in this association has not been defined. T3 may play a critical role in T cell activation. Monoclonal antibodies reactive with T3 can provide one of the two requisite signals required for T cell activation (13-15). Thus, such antibodies can induce T cell activation in a manner analogous to that noted with antigen or anti-receptor antibodies. This transmembrane activation signal is mediated by an increase in cytoplasmic free calcium (16). The studies reported here examined the association between T3 and antigen receptor-like molecules expressed on a functional human T cell line, Jurkat, using mutants of Jurkat. These studies demonstrate that there appears to be an obligate requirement for the coexpression of T3 and the antigen receptor. Moreover, This work was supported in part by grant AI 14104 from the U. S. Public Health Service. J. Stobo is an investigator and A. Weiss, an associate, of the Howard Hughes Medical Institute.