CROSS-LINKING OF CD26 BY ANTIBODY INDUCES TYROSINE PHOSPHORYLATION AND ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE

CD26, a T-cell activation antigen that has dipeptidyl peptidase IV act ivity in its extracellular domain and has also been shown to play an i mportant role in T-cell activation. The earliest biochemical events se en in stimulated T lymphocytes activated through the engagement of the T-cell receptor (TCR) is the tyrosine phosphorylation of a panel of c ellular proteins. In this study we demonstrate that antibody-induced c ross-linking of CD26 in CD26-transfected Jurkat cells induced tyrosine phosphorylation of several intracellular proteins with a similar patt ern to that seen after TCR/CD3 stimulation. Herbimycin A, an inhibitor of the src family protein tyrosine kinases dramatically inhibited thi s CD26-mediated effect on tyrosine phosphorylation. Major tyrosine pho sphorylated proteins were identified by immunoblotting, and included p 56(lck), p59(fyn), zeta associated protein-tyrosine kinase of 70000 MW (ZAP-70), mitogen-activated protein (MAP) kinase, c-Cbl, and phosphol ipase C gamma. CD26-induced tyrosine phosphorylation of MAP kinase cor related with increased MAP kinase activity. In addition, CD26 was cost imulatory to CD3 signal transduction since co-cross-linking of CD26 an d CD3 antigens induced prolonged and increased tyrosine phosphorylatio n in comparison with CD3 activation alone. We therefore conclude that CD26 is a true costimulatory entity that can up-regulate the signal tr ansducing properties of the TCR.