Molecular analysis of CD26-mediated signal transduction in T cells

CD26 or dipeptidylpeptidase IV (DPP IV) is a cell surface protease involved in T cell activation. It is a type II transmembrane glycoprotein consisting of a large extracellular part, a single transmembrane region and a short cytoplasmic tail without any common signalling motifs. To eluciate the mechanisms involved in CD26-mediated signalling we have constructed C-terminal deletion mutants of the human CD26 molecule and transfected them into murine T cell hybridomas. Stimulation experiments show that most of the extracellular part of CD26 can be deleted without affecting its costimulatory activity. The membrane proximal glycosylation rich region of CD26 is sufficient to transduce costimulatory signals. Activation of T cells via CD26, however, is not mediated by the important T cell receptor associated adaptor proteins LAT and TRIM as shown in colocalization assays.