title: The costimulatory activity of the CD26 antigen requires dipeptidyl peptidase IV enzymatic activity.
abstract: T cells have been shown to express CD26, a known ectoenzyme with dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) activity in its extracellular domain. CD26 can also deliver a second costimulatory signal and contribute to T-cell activation. In an earlier study, we established CD26-transfected Jurkat T-cell lines and demonstrated that monoclonal antibody-mediated crosslinking of CD26 and CD3 induced interleukin 2 (IL-2) production. To determine the contribution of DPPIV enzymatic activity to the costimulatory activity of CD26, human CD26 cDNA was mutated so that active-site serine was replaced by alanine. The mutant CD26 antigen lacked DPPIV enzyme activity but still retained reactivity with three anti-CD26 monoclonal antibodies directed against distinct epitopes of CD26. After stimulation with a combination of anti-CD26 and anti-CD3 antibodies, wild-type CD26 (DPPIV+)-transfected Jurkat cells produced substantially more IL-2 than did mutant CD26 (DPPIV-) or CD26- control transfectants. Nevertheless, the mutant CD26-transfected cells still produced significantly more IL-2 than did CD26- control transfectants. These results suggest that DPPIV activity plays an important but not absolute role in the co-stimulatory activity of CD26 in this system. We also found that wild-type CD26 (DPPIV+) transfectants produced more IL-2 than mutant CD26 (DPPIV-)-transfected cells or CD26- control transfectants when triggered by stimuli not involving CD26, such as anti-CD3 and phorbol ester. These results suggest that the DPPIV activity of CD26 functions to augment the cellular responses of CD26-transfected Jurkat cells to external stimuli mediated by CD26 and/or the CD3/T-cell receptor complex, thus enhancing IL-2 production.
authors.affiliation: Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Kameoka
authors.forename: A
authors.initials: A
authors.lastname: Yaron
authors.forename: S F
authors.initials: SF
authors.lastname: Schlossman
authors.forename: C
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D017252:CD3 Complex / Q000502:physiology; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism*; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000939:Epitopes; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D013755:Tetradecanoylphorbol Acetate