CD3-ZETA DEPENDENCE OF THE CD2 PATHWAY OF ACTIVATION IN LYMPHOCYTES-T AND NATURAL-KILLER-CELLS

In T lymphocytes, signal transduction through the CD2 adhesion molecule requires surface expression of the CD3-Ti T-cell receptor (TCR) complex. In contrast, in natural killer (NK) cells, CD2 functions in the absence of a TCR. Because the TCR on T lymphocytes and the CD16 low-affinity IgG Fc receptor (Fc-gamma receptor type III) complex on NK cells share a common CD3-zeta subunit, we reasoned that CD3-zeta may be critical for CD2 signaling in T lymphocytes and NK cells. Here we show that transfection of a cDNA encoding a transmembrane form of CD16 into TCR- variants of the Jurkat T-cell line results in CD16 expression in association with endogenous CD3-zeta homodimers and restores CD2 signaling function. To test directly the role of CD3-zeta in CD2 triggering, we then transfected human CD2 into each of two murine T-T hybridomas that express TCRs containing either a full-length CD3-zeta subunit or a truncated CD3-zeta subunit incapable of transducing signals. Despite expression of equivalent surface levels of TCR, CD2-mediated signaling is seen only in the T cells containing wild-type CD3-zeta. These findings show that (i) CD16 on NK cells is functionally equivalent to the TCR on T lymphocytes for coupling CD2 to signaling pathways and (ii) CD2 signal transduction depends upon the CD3-zeta subunit of the TCR complex and, by inference, the CD3-zeta subunit of the CD16 complex.