Involvement of T3 and T8 molecules in human T cell receptor function. Anti-T3 or anti-T8 antibodies do not block the antigen-dependent activation of a subset of alloreactive cytolytic T cell precursors

In the present study, we have analyzed the effects of anti-T8 and anti-T3 monoclonal antibodies (mAb) on the generation of human allospecific cytolytic T lymphocytes (CTL). A sensitive limiting dilution microculture system, in which graded numbers of responder T cells were added to 10⁵ irradiated allogeneic spleen cells and saturating amounts of exogeneous interleukin 2, has been employed to provide minimal estimates of the frequencies of alloreactive CTL precursors (CTL-P) present in T lymphocyte populations freshly isolated from peripheral blood. Addition of anti-T8 or anti-T3 mAb at the onset of micro mixed lymphocyte culture containing peripheral blood T lymphocytes as responding cells caused a 65-80% reduction in the frequency of specific CTL-P which proliferate under these conditions. Moreover, in most instances (> 80%) the cytolytic activity of those CTL-P which underwent clonal expansion in the presence of either anti-T8 or anti-T3 mAb was found to be resistant to inhibition by corresponding mAb added during the cytolytic assay. In addition, a great degree of overlap existed between microcultures resistant to anti-T3 and those resistant to anti-T8 mAb. In contrast, neither antibody had any inhibitory effect when added later to the cultures, presumably because at this stage CTL-P had been already triggered by alloantigens. Taken together our data indicate that the heterogeneity in the susceptibility to inhibition by anti-T3 or anti-T8 mAb, previously observed at the level of CTL clones, is predetermined already at the level of peripheral blood CTL-P.