Activating interactions in human NK cell recognition: the role of 2B4-CD48

2B4 is a cell surface glycoprotein of the immunoglobulin superfamily struct urally related to CD2-like molecules. It was originally identified in the m ouse as a receptor that mediates nonMHC-restricted cytotoxicity by NK cells and GD8(+) T cells. Recently, 2B4 was shown to bind CD48 by molecular bind ing assays and surface plasmon resonance. Here, we have investigated the ce ll surface expression, biochemical characteristics and function of human 2B 4. Our results show that 2B4 is expressed not only on NK cells and CD8(+) T cells, but also on monocytes and basophils, indicating a broader role for 2B4 in leukocyte activation. In NK cells, engagement of 2B4 with a specific monoclonal antibody or with CD48 can trigger NK cell-mediated cytotoxicity . The contribution of 2B4-CD48 interaction ts target cell lysis by differen t NK cell clones varies, probably dependent on the relative contribution of other receptor-ligand interactions. In T cells and monocytes, ligation of 2B4 does not lead to T cell or monocyte activation. Thus, it appears that t he primary function of 2B4 is to modulate other receptor-ligand interaction s to enhance leukocyte activation.