title: Unchanged signaling capacity of mutant CD26/dipeptidylpeptidase IV molecules devoid of enzymatic activity.
abstract: CD26 is a proteolytic enzyme (dipeptidylpeptidase IV) that defines an alternative activation signal for human T lymphocytes. Crosslinking of CD26 via monoclonal antibodies triggers proliferation and cytotoxicity in CD26-positive T cells or provides costimulatory signals for these cells. Because there is some debate about whether the enzymatic activity plays a role in activation via CD26 we have here generated a mutant CD26 molecule devoid of enzymatic activity. After transfection into T cell receptor-positive recipient T cells, such mutant molecules were tested for their signaling capacity compared to that in the wildtype molecules. The response of transfected clones to direct stimulation with anti-CD26 antibodies and to costimulation via CD26 was variable and not solely dependent on the amount of CD26 and T cell receptor expressed on the T cells. Several mutant transfectants were more easily triggered via CD26 than cells transfected with the wildtype molecule. These data demonstrate that the enzymatic activity of CD26 is not required for its T cell activating or costimulating properties.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Steeg
authors.forename: U
authors.initials: U
authors.lastname: Hartwig
authors.forename: B
authors.initials: B
authors.lastname: Fleischer
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D002384:Catalysis; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D017252:CD3 Complex; D011971:Receptors, Immunologic; D018819:Dipeptidyl Peptidase 4