The role of L3T4 in T cell activation: L3T4 may be both an Ia-binding protein and a receptor that transduces a negative signal.
The T cell surface molecules Lyt-2 and L3T4 are strongly correlated with the class of MHC gene product recognized by the T cell bearing them. The L3T4 molecule has been proposed to play a role in enhancing recognition of antigen:Ia by specific T cells. In the present experiments, we have explored the role of L3T4 in T cell activation by examining the effects of the L3T4-specific monoclonal antibody GK1.5 on T cell responses in the presence or absence of class II-MHC gene products. Our studies show that GK1.5 inhibits T cell activation in the absence of class II-MHC gene products, while antibodies to other T cell surface molecules do not transduce negative signals to the same cells. We interpret our results as suggesting a signaling role for L3T4 and, by inference, for Lyt-2 as well. We would propose that L3T4 molecules on the class II-restricted T cell initiate the interaction between the L3T4+ T cell and its class II-MHC gene product bearing target cell (B cell, APC). This initial contact is important in allowing a finite time for antigen, Ia, and the T cell receptor to form an activating complex, which in turn transduces a dominant on signal to the cell. In the absence of specific antigen, or if the class II-bearing cell is of the wrong MHC genotype, so that the antigen:Ia receptor is not aggregated, then the association of L3T4 with class II molecules transduces a net negative signal to the T cell. We suggest that this negative signal is responsible for T cell:target cell deconjugation under these circumstances. Thus, we would propose that L3T4 initiates T cell:Ia-bearing cell interactions and, a finite time later, signals the T cell to discontinue the interaction unless a stimulating level of the antigen:Ia complexes for which the T cell's receptor is specific is present.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology*; D002118:Calcium / Q000032:analysis; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D002118:Calcium