Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85

Recruitment of CD2 to the immunological synapse in response to antigen is dependent on its proline- rich cytoplasmic tail. A peptide from this region ( CD2: 322 - 339) isolated CMS ( human CD2AP); a related protein, CIN85; and the actin capping protein, CAPZ from a T cell line. In BIAcore(TM) analyses, the N- terminal SH3 domains of CMS and CIN85 bound CD2: 322 - 339 with similar dissociation constants ( K(D) = similar to 100 muM). CAPZ bound the C-terminal half of CMS and CIN85. Direct binding between CMS/ CIN85 and CAPZ provides a link with the actin cytoskeleton. Overexpression of a fragment from the C- terminal half or the N- terminal SH3 domain of CD2AP in a mouse T cell hybridoma resulted in enhanced interleukin-2 production and reduced T cell receptor down-modulation in response to antigen. These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/ CIN85 and CAPZ.