Coaggregation of the T-cell receptor with CD4 and other T-cell surface molecules enhances T-cell activation.
The CD4 molecule, expressed by T cells restricted by class II major histocompatibility complex (MHC) molecules, is believed to play a role in T-cell activation. We have previously suggested that CD4 interacts with the T-cell receptor for antigen (TCR) and with class II MHC and that this dual interaction stabilizes the bond between the TCR and antigen in association with MHC. To investigate the contribution of CD4-TCR interaction, we have used the murine monoclonal anti-TCR V beta 8 antibody F23.1 to activate cloned T cells. Weak activation by soluble biotinylated F23.1 was markedly enhanced by crosslinking with either avidin or with anti-immunoglobulin (anti-Ig). The monoclonal anti-L3T4 antibody GK1.5, which normally inhibits the activation induced by F23.1, did not inhibit when GK1.5 and F23.1 were coaggregated on T cells by anti-Ig, and in many experiments activation was enhanced. Coaggregation of anti-Thy-1.2, anti-H-2Kk, or anti-LFA-1 with F23.1 also enhanced T-cell activation, although, unlike GK1.5, these antibodies in soluble form had no effect on the response to F23.1. These results are consistent with a model for T-cell activation that proposes a primary interaction between L3T4 and the TCR to stabilize TCR complexes and so to enhance T-cell activation. A related but less specific accessory role for other T-cell surface molecules is also suggested. We propose that the cellular interaction that leads to physiological T-cell activation not only achieves TCR ligation but also promotes through their ligation or redistribution the interaction of other T-cell surface molecules, all of which contribute to the overall strength of the activation signal.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte; D046911:Macromolecular Substances; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell