Cell surface structures involved in T cell activation.

Abstract

We have discussed four specific models which provide different kinds of information about the requirements for T cell activation. The first utilized a CTL clone designated L3, which is reactive specifically with Ld alloantigen, to study the involvement of the associative recognition structure Lyt-2 in cytolysis. The apparent requirements for activation of this CTL clone differ depending on whether the target cells bear specific alloantigen or are hybridoma cells which express on their cell surface a clonotypic antibody which reacts specifically with the L3 T cell receptor for antigen. When the antigen receptor reacts with alloantigen on the allogeneic target cell, cytolysis is inhibited by anti-Lyt-2 antibody. However, when the clonotypic antibody of the target cell reacts with the antigen receptor of the T cell, cytolysis is much less inhibited by anti-Lyt-2 antibody. The antigen receptor seems to be responsible for the specificity of both these interactions but the avidity of the interaction between CTL and target cell seems to differ in the two situations. Evidence that participation of the L3T4 associative recognition structure on HTL is less important for cloned T cells which have higher affinity antigen receptors was provided by the second model system which used cloned HTL selected for optimal responses to different concentrations of nominal antigen. Proliferative responses of those clones which responded to lower antigen concentrations were less readily inhibited by anti-L3T4 mAb. Evidence provided by these two model systems is consistent with the concept that associative recognition structures are of lesser importance for T cell activation for those T cells which have higher affinity antigen receptors. In the third model system, we have identified several monoclonal antibodies which augment proliferative response of cloned T cells to sub-optimal amounts of IL-2, probably by reacting with the antigen receptor or with the associated Leu-4/T3 structure. The reactivity patterns of these antibodies indicate that several different epitopes are being recognized. Some appear to be clonotypic although they do not block functional activity of the clone with which they react. Others react with all T clones which we have tested. Several of these react with a cell surface antigen which is expressed at about the same level as the clonotypic structures: these antibodies may react with the murine equivalent of the human Leu-4/T3 molecular complex. One of the "pan-T cell" antibodies which augments IL-2-induced T cell proliferation appears to react with Thy-1; this antibody is similar to one described recently by Gunter et al. (1984).(ABSTRACT TRUNCATED AT 400 WORDS)