CHARACTERIZATION OF ADENOSINE-DEAMINASE BINDING TO HUMAN CD26 ON T-CELLS AND ITS BIOLOGIC ROLE IN IMMUNE-RESPONSE

CD26, a T cell activation Ag, also known as dipeptidyl peptidase IV, i s directly associated with adenosine deaminase (ADA) on the surface of T cells and T cell lines. In the present study, we examined both the binding of ADA to CD26 and the functional consequences of this interac tion. We found that ADA was associated with CD26 on T cell lines lacki ng either ADA or dipeptidyl peptidase IV enzymatic activity, indicatin g that the association between dipeptidyl peptidase IV and ADA did not require enzymatic activity. Moreover, using immunoelectron microscopy , we demonstrated that CD26 and ADA co-localized on the cell surface, but not inside cells, suggesting that CD26 did not transport ADA to th e surface. In keeping with this observation, we showed that human CD26 -transfected murine pre-B cell lines lacking human ADA acquired ADA fr om an extracellular source. More importantly, adenosine in the absence of cell surface ADA inhibited T cell proliferation and IL-2 productio n induced by various stimuli. On the other hand, cells expressing ADA and CD26 on the surface were much more resistant to the inhibitory eff ect of adenosine. These data suggest that DA on the cell surface is in volved in an important immunoregulatory mechanism by which released AD A binds to cell surface CD26, and this complex is capable of reducing the local concentration of adenosine.