Two monoclonal anti-CD3 antibodies can induce different events in human T lymphocyte activation

Two monoclonal antibodies, WT32 and CLB-T3/4.2a, directed against the CD3 complex were used to study the mechanism of activation of human peripheral T lymphocytes. WT32, a mouse monoclonal IgG2a antibody with a low avidity (much less than OKT3) for the CD3 complex, effectively induces mitogenesis of purified T lymphocytes when used in the 1 ng-10 micrograms range in the presence of monocytes or recombinant interleukin 2 (IL2). In contrast, CLB-T3/4.2a, a mouse monoclonal antibody of the same isotype with a high avidity (much greater than OKT3) for the CD3 complex, induces IL2 receptor expression and IL2 responsiveness only at very low concentrations (less than 5 ng/ml), yet in the presence of monocytes this antibody induces proliferation within a similar dose range as WT32. Apparently, in the absence of accessory cells which can cross-link the antibody CD3 complexes, the binding properties (avidity) of an antibody and thereby the number of receptors that are occupied are important parameters for induction of IL2 responsiveness. Furthermore, we show that Ca2+ mobilization only occurs when the cells are stimulated by saturating amounts of antibody, so that, when the conditions are optimal for the induction of IL2 responsiveness, no Ca2+ mobilization will be detected