Calcium Mobilization and Enhanced Natural Killer Function in Large Granular Lymphocytes Result from Cross-Linking the CD2 E-Rosette and CD16 Fc-Receptor

摘要

The binding of monoclonal antibodies that recognize the CD2 E-rosette receptor results in T-cell proliferation, and in increased killing by cytotoxic T-lymphocytes and large granular lymphocytes (LGL). We recently found that in the case of LGL, a single antibody directed against 'internal' activation epitopes of the CD2 structure was sufficient to increase intracellular calcium concentration Ca(2+), whereas in the case of T-cells, combinations of CD2 antibodies against both 'internal' and 'external' epitopes were required. The purpose of the present study was to evaluate the CD2 panel of antibodies to further define the mechanisms of LGL activation via the CD2 pathway. Our results indicate that only antibodies of the IgG3 isotype are capable of directly stimulating LGL calcium mobilization and natural killing, and furthermore, that this stimulation is dependent upon both the Fc and F(ab')2 regions of the antibody, indicating a requirement for the simultaneous bridging of the CD2 E-rosette and CD16 FcR(low) structures. Using a sensitive assay to measure Ca(2+)i in single cells, we previously found that stimulation of peripheral blood mononuclear cells (PBMC) with a combination of mitogenic CD2 antibodies resulted in a biphasic Ca(2+)i response consisting of an early low-magnitude response in LGL, and a delayed high-magnitude response in T-cells. Reprints. (AW)