DIPEPTIDYL-PEPTIDASE IV CD26 ON T-CELLS - ANALYSIS OF AN ALTERNATIVE T-CELL ACTIVATION PATHWAY/

CD26 is a proteolytic enzyme (dipeptidyl-peptidase TV) with a wide tis sue distribution and a unique specificity that was already described 2 7 years ago. CD26 is expressed on a fraction of resting T cells at low density but is strongly upregulated following T-cell activation. Rece nt results indicate that CD26 is a multifunctional molecule that may h ave important functions on T cells and in the immune system. It is ass ociated with molecules of immunological importance such as the protein tyrosine phosphatase CD45 and adenosine deaminase (ADA) on the cell s urface. Synthetic inhibitors of the enzymatic activity of CD26 have be en shown to suppress certain immune reactions in vitro and in vivo. An interesting feature of CD26 is its ability to transmit a transmembran e signal to trigger functional programs in T cells. This triggering re quires crosslinking of CD26 on a cell membrane. The enzymatic activity of CD26 is not obligatory for the activation of T cells via CD26. Sin ce CD26 is a type II membrane protein with only six intracellular amin o acids, it must deliver its signal via a signal-transducing molecule. Signaling is dependent on the expression of the T-cell receptor (TCR) complex with a special need for a functional zeta-chain. In this cont ext the zeta-chain of the TCR complex is required for CD26-mediated si gnaling but, in contrast to other co-stimulatory molecules such as the CD2 molecule, is not sufficient for triggering the T cell.