Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions.

Abstract

The M7/14 monoclonal antibody (MAb) has previously been shown to block xenogeneic cytolytic T lymphocyte-(CTL) mediated killing by binding to the CTL rather than the target cell. It defines a novel surface antigen, termed LFA-1, with polypeptide chains of 180,000 and 95,000 M1 (1). The mechanism of this blockade and the effects of M7/14 on other T and B lymphocyte functional responses have been investigated here. Blockade of CTL-mediated killing is given by purified M7/14 MAb, and is not due to trivial mechanisms such as toxicity or agglutination. M7/14 blocks CTL directed to allogeneic and anti-modified self as well as xenogeneic determinants. Blockade occurs at the recognition-adhesion step, as shown by inhibition of CTL-target cell conjugate formation.M7/14 antibody was also shown to block a variety of other T cell functions: the mixed lymphocyte response (both in xenogeneic and allogeneic systems), antigen-specific T cell proliferation, and T cell-dependent plaque-forming cell responses, but not T cell-independent plaque-forming cell responses or LPS-induced B cell proliferation.Inhibition of both CTL and MLR function was extremely potent, occurring at MAb concentrations as low as 0.5 µg/ml. Inhibition of the MLR occurs in the 1st day of 6-day cultures. The data suggest that LFA-1 participates in or is closely associated with a number of different T lymphocyte functional pathways. LFA-1 appears crucial for the adhesive interaction between CTL and target cells, and it is possible that its importance in T helper and proliferative responses is also related to intercellular interactions.