The adenosine deaminase-binding region is distinct from major anti-CD26 mAb epitopes on the human dipeptidyl peptidase IV(CD26) molecule

CD26 or dipeptidyl peptidase IV (DPP-IV) is a cell surface protease involve d in T cell activation, Monoclonal antibodies (mAbs) directed against the C D26 molecule are able to stimulate CD26-expressing T cells, Although many d ifferent CD26-specific mAbs exist which are able to provide a triggering si gnal in T cells, little is known about their specific epitopes on the CD26 molecule. Whereas some mAbs were shown to compete with each other and to in hibit the association of adenosine deaminase (ADA) and human immunodeficien cy virus 1 (HIV-1)-derived Tat protein with CD26, other CD26-specific mAbs obviously bind to distinct regions on DPP-IV. In the present study we have generated truncated versions of the human CD26 molecule and expressed them in COS-1 cells to study the binding pattern of a panel of 14 CDS6-specific mAbs in confocal microscopy and, thus, correlated the CD26-specific mAbs ep itopes with the binding region of ADA. We show that the majority of anti-CD 26 mAbs is directed against the glycosylation-rich region of the molecule w hereas the ADA-binding site could be located in the cysteine-rich region of DPP-IV, In contrast to binding experiments with purified ADA, which reveal ed a specific association with CD26 on CD26-positive Jurkat cells, HIV-deri ved Tat protein did not interact specifically with CD26 on transfected Jurk at cells, nor could Tat binding be competed by anti-CD26-specific mAbs. (C) 1999 Academic Press.