A NOVEL FUNCTION-ASSOCIATED MOLECULE RELATED TO NON-MHC-RESTRICTED CYTOTOXICITY MEDIATED BY ACTIVATED NATURAL-KILLER-CELLS AND T-CELLS

NK cells and IL-2-propagated splenic T cells mediate non-MHC-restricte d cytotoxicity. The molecules involved in this process are not well de fined. We describe a novel 66-kDa cell surface molecule called 2B4 tha t is expressed on cells that mediate non-MHC-restricted cytotoxicity. All resting and rIL-2 cultured NK cells and a significant number of T cells cultured in high doses of rIL-2 are 2B4+. In fresh as well as cu ltured spleen cells, all non-MHC-restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of n on-MHC-restricted killing, the 2B4 molecule is also involved in modula tion of their function. In the presence of anti-2B4, the lytic activit y of cultured NK cells and non-MHC-restricted T cells against a wide v ariety of FcR- and FcR+ targets is greatly augmented. Anti-2B4 is also able to transduce other signals in IL-2-activated NK cells such as IF N-gamma secretion and granule exocytosis. In addition, 2B4+ T cells ca n specifically lyse the 2B4 hybridoma cells. Unlike many other activat ion and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conver sely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 m olecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC-restricted k illing.