Activation of human T lymphocytes through CD3 and CD2 (T11) with anti-CD3-coupled sheep erythrocytes

Abstract

Proliferative activation of T lymphocytes depends on cell-cell cooperation, i.e. interactions between specific cell surface receptors and their ligands. My co-workers and I have recently shown that an activating signal is mediated by interaction between the T cell surface antigen CD2 (T11) and its ligand on sheep erythrocytes (SE), the T11 target structure (T11TS), which is the homologue to the human LFA-3 antigen. Here I demonstrate that the anti-CD3 monoclonal antibody (MoAb) UCHT1 coupled to SE (SE-UCHT1) most efficiently induces accessory cell (AC)-independent T cell proliferation, and that SE can substitute for AC in stiumulation with phytohaemagglutinin (PHA). Inhibition studies with MoAb suggest that (1) concurrent stimulation of CD3 and CD2 is essential for interleukin 2 production and proliferation, since SE-UCHT1 treated with the anti-T11TS MoAb L180/1 are not mitogenic; (2) proximity of CD3 and CD2 is required during the stimulation, since a mixture of SE exposing either anti-CD3 or T11TS is not mitogenic; and (3) that T cell-AC interactions involving LFA-1 can be replaced by LFA-3-CD2 interactions, since the anti-LFA-1 MoAb 60.3 does not inhibit the SE-UCHT1 response, and only partly the SE + PHA response. These results demonstrate a functional linkage between the CD3 and CD2 structures, making accessory LFA-1 signals superfluous in proliferative activation of human resting peripheral T cell.