Analysis of the molecular mechanism involved in 2B4-mediated NK cell activation: evidence that human 2B4 is physically and functionally associated with the linker for activation of T cells

While 2B4 is a well-known surface receptor involved in NK cell triggering a nd induction of cytotoxicity against CD48-positive target cells, little is known about the downstream events which lead to NK cell activation. In this study we show that, in normal human NK cells, 284 constitutively associate s with the linker for activation of T cells (LAT). Antibody-mediated engage ment of 284 resulted in tyrosine phosphorylation not only of 284 but also o f the associated LAT molecules. Moreover, tyrosine phosphorylation of LAT l ed to the recruitment of intracytoplasmic signaling molecules including pho spholipase Cy and Grb2. These data support the concept that 2B4 may mediate NK cell triggering via a LAT-dependent signaling pathway.