Glycosylation of the T-Cell Antigen-Specific Receptor and its Potential Role in Lectin-Mediated Cytotoxicity

Cytotoxic T lymphocytes (CTLs) normally destroy only those cells (``target cells'') whose surface antigens they recognize. However, in the presence of lectins such as Con A, CTLs destroy virtually any cell, regardless of its antigens. The oligosaccharides of the T-cell antigen-specific receptor, a dimeric surface glycoprotein composed of disulfide-linked α and β subunits, are of interest because of their potential involvement in this lectin-dependent cytotoxic activity. We report here that three or four asparagine-linked oligosaccharides could be enzymatically removed from each of the receptor subunits expressed by a cloned line of murine CTLs (clone 2C), consistent with the presence of glycosylation sites deduced from cDNA sequences of the α and β genes expressed in this clone. All the N-linked glycans on the α subunit were of the complex type (i.e., resistant to endoglycosidase H), but the β subunit carried two or three endoglycosidase H-sensitive (high-mannose) oligosaccharides. High-mannose glycans can bind tightly to Con A and, indeed, this lectin was found to bind specifically to solubilized 2C T-cell receptor. The Con A-dependent cytotoxic activity of clone 2C, but not of other CTL clones, was inhibited by a monoclonal antibody (1B2) that is specific for the T-cell receptor of clone 2C. Antibody 1B2 also inhibited clone 2C cytotoxicity mediated by phytohemagglutinin, lentil-lectin, and wheat-germ agglutinin. These results suggest that, although lectin-dependent lysis of target cells by CTLs is antigen nonspecific, the cytolytic activity can be triggered by binding of the lectin to the T-cell antigen-specific receptor.