THE RECEPTOR FUNCTION OF CD2 IN HUMAN CD2 TRANSGENIC MICE IS BASED ONHIGHLY CONSERVED ASSOCIATIONS WITH SIGNAL-TRANSDUCTION MOLECULES

The activation of human T cells via CD2 in response to mitogenic monoc lonal antibodies (mAbs) typically requires that one mAb is specific fo r an epitope within the N-terminal Ig domain of CD2 and the other for a partially hidden epitope. We have examined the proliferative respons e of human T cells and human CD2 (huCD2) transgenic murine T cells to two novel CD2 monoclonal antibodies, AICD2.M1 and AICD2.M2, and have p artially mapped the epitopes of these and other mitogenic CD2-specific monoclonal antibodies by way of recognition of CD2:CD58 chimeric prot eins possessing either the N-terminal or the membrane proximal immunog lobulin domains of CD2. To understand the molecular basis of prolifera tion in huCD2 transgenic murine T cells, the interactions of huCD2 wit h signaling proteins in murine T cells were analyzed, The transgenic h uCD2 molecule was found to interact with the murine tyrosine kinases p 56(lck) and p59(fyn) and the CD3-epsilon and zeta chains of the TCR/CD 3 signaling complex and to coimmunoprecipitate tyrosine phosphatase ac tivity. These molecular associations resemble the situation in human T cells and suggest that human CD2 couples to the same signal transduct ion pathways in humans and transgenic mice. (C) 1997 Academic Press.