1514 Activation of Human T Cells by Monoclonal Antibody

Considerable progress has been made in the delineation of human functional T cell subsets and in the identification of T cell-specific and -associated antigens (reviewed in 1 and 2). Some of these antigens are closely involved in human T cell activation and proliferation. The importance of the T3 /Ti (Ti, putative T cell receptor) 1 complex in antigen-specific T cell activation has recently been reviewed (3, 4). Although this is a major activation pathway, an alternative antigen-independent pathway involving the T11 antigen, the sheep erythrocyte receptor, has been proposed (5, 6). Two unique anti-T11 monoclonal antibodies (mAb) in combination were shown to activate T cells by Ca 2+ influx, and to induce T cells to proliferate. This pathway was shown to be related to the T3 /T i complex in that modulation of the T3 /T i complex inhibited the effects by these two mAb. Recently, we demonstrated that anti-T3 mAb, in collaboration with tumor promoter 12-0-tetradecanoyl phorbol-13-acetate (TPA), induced human T cells to express interleukin-2 (IL-2) receptors, to secrete IL-2, and to proliferate (7). This process was independent of monocytes. Herein, other ant i -T cell mAb were screened for their effects on T cell activation in this system, mAb 9.3, reactive with a disulfide-bonded dimer of a 44 kilodalton (kD) polypeptide on a major T cell population, was found to induce T cell activation and proliferation in collaboration with TPA, in a manner similar to that of the anti-T3 mAb. Modulation of the T3 /T i complex did not inhibit the effects induced by mAb 9.3 and TPA. Thus, antigen 9.3 is involved in a novel activation pathway used by a major T cell population.