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-restricted cytotoxicity. The molecules involved in this process are not well defined. We describe a novel 66-kDa cell surface molecule called 2B4 that 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 cultured spleen cells, all non-MHC-restricted cytotoxicity is contained within the 2B4+ population. In addition to defining cells capable of non-MHC-restricted killing, the 2B4 molecule is also involved in modulation of their function. In the presence of anti-2B4, the lytic activity of cultured NK cells and non-MHC-restricted T cells against a wide variety 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 IFN-gamma secretion and granule exocytosis. In addition, 2B4+ T cells can specifically lyse the 2B4 hybridoma cells. Unlike many other activation and adhesion molecules (such as murine CD2, LFA-1, and CD16), 2B4 expression is restricted to cells that mediate NK-like killing. Conversely, highly activated T cells that do not express 2B4 do not mediate non-MHC-restricted killing. Together these data suggest that the 2B4 molecule is likely to be a part of a receptor complex or a component of signal-transducing complex on cells that mediate non-MHC-restricted killing.
Garni-Wagner
B A
BA
Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas 75235.
Purohit
A
A
Mathew
P A
PA
Bennett
M
M
Kumar
V
V
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface