Human CD48 ELISA Kit

While 2B4 is a well-known surface receptor involved in NK cell triggering and 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 associates with the linker for activation of T cells (LAT). Antibody-mediated engagement of 284 resulted in tyrosine phosphorylation not only of 284 but also of the associated LAT molecules. Moreover, tyrosine phosphorylation of LAT led to the recruitment of intracytoplasmic signaling molecules including phospholipase Cy and Grb2. These data support the concept that 2B4 may mediate NK cell triggering via a LAT-dependent signaling pathway.

T cells bearing chimeric antigen receptors (CARs) are broadly categorised into first-and second-generation receptors. Second-generation CARs contain a co-stimulatory signalling molecule and have been shown to secrete IL-2, undergo greater proliferation and to have enhanced persistence in vivo. However, we have shown that T cells bearing a first-generation CAR containing a CD19-targeting scFv (single-chain variable fragment) and the CD3 zeta-signalling domain are able to produce IL-2 upon co-culture with CD19(+) B-cell lymphomas independent of CD28 activity. Here, we report that signalling through endogenous CD2 following ligation with its ligands, CD48 in mouse and CD58 in humans, drives IL-2 production by first-generation CD19-specific CAR. Moreover, the high levels of IL-2 produced by human T cells engrafted with a second-generation CD28-containing CAR during target-cell recognition are dependent to a degree upon CD2 receptor activity. These observations highlight the fact that the functional activity induced by T-cell-expressed CARs is dependent upon endogenous 'natural' receptor interactions. A deeper understanding of the role of these activities will serve to further refine the design of future CARs to either exploit or avoid these interactions.