Diabetogenic T-cell clones recognize an altered peptide of chromogranin A.
Chromogranin A (ChgA) has been identified as the antigen target for three NOD-derived, diabetogenic CD4 T-cell clones, including the well-known BDC-2.5. These T-cell clones respond weakly to the peptide WE14, a naturally occurring proteolytic cleavage product from ChgA. We show here that WE14 can be converted into a highly antigenic T-cell epitope through treatment with the enzyme transglutaminase (TGase). The WE14 responses of three NOD-derived CD4 T-cell clones, each with different T-cell receptors (TCRs), and of T cells from BDC-2.5 TCR transgenic mice are increased after TGase conversion of the peptide. Primary CD4 T cells isolated from NOD mice also respond to high concentrations of WE14 and significantly lower concentrations of TGase-treated WE14. We hypothesize that posttranslational modification plays a critical role in the generation of T-cell epitopes in type 1 diabetes.
Denver School of Medicine and National Jewish Health, Denver, Colorado, USA.
Thomas
T
Delong
Rocky L
RL
Baker
Jing
J
He
Gene
G
Barbour
Brenda
B
Bradley
Kathryn
K
Haskins
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D002850:Chromatography, Gel; D053379:Chromogranin A / Q000276:immunology*; D005434:Flow Cytometry; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011503:Transglutaminases / Q000378:metabolism
D053379:Chromogranin A; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011503:Transglutaminases