Possible involvement of the T4 molecule in T cell recognition of class II HLA antigens. Evidence from studies of CTL-target cell binding.

Abstract

The potential role of the T4 molecule in functional cell-cell interactions between target cells and human cytotoxic T lymphocyte (CTL) clones that are specific for HLA class II alloantigens encoded by the SB locus was tested. There were marked differences (> 30-fold) between the 7 SB-specific clones studied with respect to their susceptibility to inhibition by anti-T4 as well as anti-T3 antibodies. The hypothesis that such variation among the clones would be due to differences in clonal affinity for antigen was tested. To quantitate differences among the CTL clones in the tightness with which they bind target cells, the clones were analyzed using a previously published assay of susceptibility of CTL-target cell conjugates to dissociation in the presence of unlabeled targets. The clones that were most susceptible to inhibition by anti-T4 and anti-T3 were the weakest target cell binders and vice versa. Anti-T4 antibody could partially induce dissociation of functional CTL-target cells conjugates in the absence of any added cold targets. For the highest affinity clone such anti-T4 antibody-induced dissociation were observed at 4.degree. C but not 23.degree. C. Evidently, the T4 molecule is functionally involved in target cell binding by CTL. Although it is easiest to demonstrate the function of the T4 molecule in low affinity clones, that function may also be operative in the high affinity clones.