IMR Press / FBL / Volume 13 / Issue 9 / DOI: 10.2741/2920

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Non-substrate peptides influencing dipeptidyl peptidase IV/CD26 activity and immune cell function
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1 Institute of Molecular and Clinical Immunology, Otto-von-Guericke-University Magdeburg, Germany
2 Institute of Biochemistry and Biotechnology, Department of Natural Sciences I, Martin-Luther-University Halle-Wittenberg, Halle, Germany
3 Leibniz Institute of Plant Biochemistry, Halle, Germany
4 University Clinic of Dermatology and Venereology, Ottovon-Guericke-University Magdeburg, Germany

*Author to whom correspondence should be addressed.

Academic Editors: Jonathan S. Duke-Cohan, Aleksi Sedo

Front. Biosci. (Landmark Ed) 2008, 13(9), 3194–3201;
Published: 1 May 2008
(This article belongs to the Special Issue Dipeptidyl peptidase IV and related molecules in health and disease)

Investigations using inhibitors of dipeptidyl peptidase IV (DP IV) activities and DP IV-/- mice indicated an immunoregulatory role of DP IV that could not be compensated by DP IV-like enzymes. The HIV-1 Tat protein was identified as the first natural inhibitor of DP IV and as immunosuppressor. This review summarizes our investigations on the identification of the amino acid motif of Tat responsible for DP IV inhibition and of endogenous DP IV-inhibitory ligands that suppress immune cell activation. Examinations on numerous peptides carrying the N-terminal Xaa-Xaa-Pro motif of Tat revealed that tryptophan at position two strongly enhanced DP IV inhibition and immunosuppression. Here, we present evidence that the thromboxane A2 receptor exposing N-terminal Met-Trp-Pro at the cell surface could be a potential endogenous, inhibitory DP IV ligand. Moreover, our data suggest that the major envelope proteins p37k of the orhtopoxviruses variola virus and vaccinia virus, as well as the B2L antigen of the parapoxvirus orf, that also carry N-terminal Met-Trp-Pro, could mediate immunosuppressive effects. Further examinations are in progress to identify new physiologic, inhibitory DP IV ligands and to enlighten the mechanism underlying the DP IV-mediated effects.

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