title: Selective binding of concanavalin A to target cell major histocompatibility antigens is required to induce nonspecific conjugation and lysis by cytolytic T lymphocytes in lectin-dependent cytotoxicity.
abstract: The exquisite immunological specificity of cytotoxic T lymphocytes-target cell (CTL-TC) conjugation and lysis is overridden in the presence of certain plant lectins. The role of concanavalin A (Con A) in lectin-dependent, CTL-mediated cytolysis (LDCC) has been investigated. Papain-treated TC are refractory to LDCC, but regain susceptibility following a 3-hr incubation without the enzyme. Papain-treated TC allowed to recover in the presence of tunicamycin (TM; an inhibitor of N-linked glycosylation), are totally refractory to LDCC. Refractoriness of TM-treated TC to LDCC is not due to an overall resistance to lysis or to lack of Con A binding, as these cells can be lysed by specifically sensitized CTL or by H-2 antibody and complement and display a sufficiently high Con A-binding capacity, indistinguishable from intact TC, probably through O-linked, cell-surface glycosyl residues. The finding that TC (TM-treated) capable of binding normal Con A quantities cannot, however, engage in lectin-dependent CTL-TC conjugation and lysis indicates that Con A must react selectively with a specific TC-surface component(s), thereby rendering the TC recognizable by effector CTL, rather than by simply bridging ("glueing") CTL and TC. Affinity absorption and elution from Sepharose-Con A beads as well as specific immunoprecipitations by antibodies against cell surface determinants, have shown effective Con A binding to TC surface components of molecular weights corresponding to 45-kDa product of the H-2K and D MHC genes and, possibly, to a 30-kDa component. Antibodies against MHC proteins but not against non-MHC surface proteins of the TC have produced effective inhibition of LDCC. This and previous investigations show that in nonspecific LDCC as in specific CTL-mediated lysis, TC-MHC determinants are involved in signaling TC recognition and lysis.
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D003208:Concanavalin A / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D006649:Histocompatibility Antigens / Q000276:immunology*; D007106:Immune Sera; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D011952:Receptors, Concanavalin A / Q000276:immunology*; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D007106:Immune Sera; D011952:Receptors, Concanavalin A; D003208:Concanavalin A; D014415:Tunicamycin