Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 44, Issue 4, Pages 1170-1180Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201343986
Keywords
BDC2; 5 T cells; Chromogranin A; I-A(g7) peptide binding motif; Type 1 diabetes
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Funding
- Canadian Institutes of Health Research (CIHR)
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The chromogranin A (ChgA) 29-42 sequence is the antigenic epitope for the BDC2.5 CD4(+) T-cell receptor in NOD mice (H-2(g7)). We have now characterized the binding register of the ChgA 29-42 peptide for the I-A(g7) molecule. Truncation of the peptide demonstrated that the KCVLEVISD sequence 34-42 is the binding register and extension of this sequence by flanking residues increased its binding affinity and antigenic capacity. We employed anti-ChgA peptide antibodies generated against different fragments of ChgA for immunostaining of pancreatic islet sections from NOD mice. A strong immuno-staining pattern was observed for the ChgA 17-38 peptide antibodies that overlap with the ChgA 29-42 sequence. Moreover, sera from diabetic NOD mice showed elevated titers of autoantibodies to the ChgA 29-42 peptide. These findings indicate that peptides from the N-terminal region of ChgA are able to induce cellular and humoral immune responses in NOD mice.
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