Phytohaemagglutinin activation of T cells through the sheep red blood cell receptor

Expression of receptors for sheep red blood cells and the ability to proliferate in response to phytohaemagglutinin (PHA) are the traditional properties of human T cells^1,2, but the function of the sheep red cell receptor (the T11 antigen) is controversial^3,4 and the mechanism of PHA-induced mitogenesis unclear. Mitogenesis involves a complex series of cell-mediated and factor-dependent interactions, but a rise in intracellular free calcium concentration, [Ca²⁺]_i, seems to be an important primary event in T-cell activation^5-7. We have now investigated the effects of three monoclonal antibodies, previously shown to inhibit mitogen-induced proliferation^3,8,9, on T-cell [Ca ²⁺]_i. We find that anti-LFA-2 and OKT11, which react with the sheep red cell receptor^8,10, have no effect on [Ca ²⁺]_i, nor do they inhibit the rise in [Ca ²⁺]_i induced by concanavalin A (Con A) or the mitogenic anti-T3 monoclonal antibody UCHT1 (ref. 11). They do, however, block PHA-induced Ca²⁺ mobilization. Anti-LFA-1, which reacts with the lymphocyte function-associated antigen^8,12, has no effect on intracellular Ca²⁺. These studies suggest that the sheep red blood cell receptor is an activation pathway for T cells and that the effects of PHA are mediated through this pathway.