The T-cell receptor associated zeta-chain is required but not sufficient for CD26 (dipeptidylpeptidase IV) mediated signaling.

CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T-cell activation. Triggering or costimulation of T-cells via CD26 was shown to be dependent on the expression of the T-cell receptor (TCR) associated zeta-chain with at least one functional immune receptor tyrosine based activation motif (ITAM). Here we tested T-cell lines expressing chimeric proteins (hCD25-zeta) consisting of human IL-2 receptor-alpha chain derived extracellular sequences (hCD25) fused to mouse-specific zeta-chain segments, for their capacity to transfer CD26 mediated signals. Although these 'minimal receptor' expressing T-cell lines were capable of transmitting signals from other costimulatory molecules (e.g. CD2), crosslinking of CD26 did not induce IL-2 secretion. Co-cross-linking of hCD25 and CD26 molecules, however, resulted in the stimulation of the T-cells. Thus, although the zeta-chain is a prerequisite for CD26 mediated signaling events, the sole expression of zeta-protein as a signaling molecule is not sufficient for CD26 mediated triggering but permits CD26 induced costimulation in TCR negative cells.