Ion channels activated by specific Ti or T3 antibodies in plasma membranes of human T cells

Abstract T lymphocytes are activated to proliferate via a surface membrane receptor recognizing the antigen/major histocompatibility complex. This membrane component is comprised of at least five polypeptide subunits, collectively termed the Ti-T3 receptor complex. A transient increase in cytosolic free calcium occurs as an early event in the T-cell activation process and is necessary for induction of the endogenous IL-2 and certain other genes. Monoclonal antibodies specific to epitopes of either the Ti or the T3 components were shown to be effective agonists, also leading to such transient rises in cytosolic free calcium and activating the lymphocytes. Here we show, using micropipette-supported bilayers formed from membranes of the human T-cell line REX, that Ti- or T3-specific antibodies cause opening of ligand gated ion channels. Both types of specific antibodies yielded similar histograms of conductance amplitudes which show a channel with a conductance of 2-3 pS in symmetrical 100 mM CaCl2 solutions. These channels allow the passage of calcium and barium ions and are blocked by lanthanum ions, suggesting that they are specific for calcium. We propose that these channels, by allowing the entry of external calcium, may account for a large fraction of the rise in intracellular calcium observed upon triggering of the Ti-T3 receptor.