Identification of novel ligand(s) for the NK cell receptor, KIR2DL4 (89.44)

Abstract

Abstract The ligands for many NK cell activating receptors remain unknown, and identification of these ligands has become a major goal for understanding the molecular basis of NK cell activation. The killer Ig-like receptor (KIR) 2DL4 is the only NK cell receptor that triggers cytokine production (IFNγ, chemokines, pro-angiogenic factors), but not cytotoxicity in resting NK cells. Several early studies reported that 2DL4 recognizes the non-classical MHC-I molecule - HLA-G. We have recently found that a soluble form of 2DL4 binds to various tumor cell lines of epithelial or fibroblast origin that lack HLA-G expression, but not to transformed hematopoietic or HLA-G positive lines. Our results demonstrate that soluble forms of HLA-G and HLA-A are both recognized by the soluble 2DL4, but binding of the 2DL4 to cell surface forms of HLA-G or HLA-A was not detected. Our studies further suggest that soluble 2DL4 or MHC-I molecules may exhibit interactions that are not characteristic of cell surface proteins and that 2DL4 recognition of the tumor cell lines is independent of surface expression of MHC-I or MHC-I like molecules.