Evidence that thymocyte-activating molecule is mouse CD26 (dipeptidyl peptidase IV).
We previously described a developmentally regulated, Mr 115,000 (reduced) and 110,000/128,000 (nonreduced) mouse T cell-activating molecule (THAM) also expressed on a variety of epithelial cell surfaces, and associated with neutral exoaminopeptidase activity. In the present study, we show that THAM is the mouse counterpart of the human T cell-activating ectoenzyme CD26 (dipeptidyl peptidase IV, DPP IV) and that highly purified THAM lacks neutral exoaminopeptidase activity. This conclusion is based on the following: 1) the N-terminal segments of the THAM Mr 110,000 and 128,000 components shared the same amino acid sequence with the rat DPP IV. These N-termini comprised a short intracytoplasmic tail of six residues followed by a downstream hydrophobic transmembrane segment. 2) THAM-specific mAb H194-112-Affi-Gel immunoadsorbent was capable of removing DPP IV enzymatic activity from mouse thymoma cell detergent extracts. 3) H194-112 reactivity pattern on developing thymocytes was found to parallel that previously reported for membrane-bound DPP IV enzymatic activity. The extent of THAM N-glycosylation, as measured by N-glycanase treatment of H194-112 immunoprecipitates, was found to be similar to that of human and rat DPP IV (i.e., approximately 20 kDa). Cross-linking experiments indicated that THAM was expressed at the cell surface as a dimer of approximately 220 kDa. Its two subunits were found to be structurally related but not identical as shown by their different Mr under nonreducing conditions and by their slightly distinct peptide profiles after proteolytic cleavage. We conclude from these data that DPP IV, in addition to its extracellular matrix receptor and ectoenzymatic functions, is a T cell-activating structure in both human and mouse species.
Vivier
I
I
Centre d'Immunologie Institut de la Santé et de la Recherche Medicale-Centre National de la Recherche Scientifique de Marseille-Luminy, France.
Marguet
D
D
Naquet
P
P
Bonicel
J
J
Black
D
D
Li
C X
CX
Bernard
A M
AM
Gorvel
J P
JP
Pierres
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry*; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000737:chemistry*; D000939:Epitopes; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011233:Precipitin Tests; D012995:Solubility; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4