The influence of valence on the functional activities of monoclonal anti-L3T4 antibodies. Discrimination of signaling from other effects.
Anti-L3T4 antibodies have different functional effects on different ligands that activate a cloned, L3T4+ helper T cell line. It is reported here that some of these effects involve positive or negative signaling induced by cross-linking L3T4 molecules, because such effects are not observed using the Fab fragment of anti-L3T4. However, the Fab fragment does inhibit responses to antigen:self class II major histocompatibility complex (MHC) and to anti-T cell receptor monoclonal antibodies directed at a particular V region epitope. The finding that the Fab fragment of anti-L3T4, which does not block binding of anti-T cell receptor V region antibodies and does not negative signal can still block activation by such antibodies suggests an intimate association of L3T4 with the T3: alpha: beta T cell receptor complex. This association may normally be induced by interaction of both structures with antigen:self class II MHC complexes. The data also support the hypothesis that cross-linking the L3T4 molecule in the absence of engagement of the T3: alpha: beta complex generates negative or inhibitory signals. Thus, L3T4 plays a central role in the process of class II MHC-restricted T cell antigen recognition and activation.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D011948:Receptors, Antigen, T-Cell