Cutting Edge: Vasostatin-1–Derived Peptide ChgA29–42 Is an Antigenic Epitope of Diabetogenic BDC2.5 T Cells in Nonobese Diabetic Mice

Authors

Enayat Nikoopour, The University of Western Ontario
Christian Sandrock, The University of Western Ontario
Katrina Huszarik, The University of Western Ontario
Olga Krougly, The University of Western Ontario
Edwin Lee-Chan, The University of Western Ontario
Emma L Masteller, University of California, San Francisco
Jeffrey A Bluestone, University of California, San Francisco
Bhagirath Singh, The University of Western Ontario

Document Type

Article

Publication Date

4-1-2011

Journal

The Journal of immunology

Volume

186

Issue

7

First Page

3831

Last Page

3835

URL with Digital Object Identifier

http://dx.doi.org/10.4049/jimmunol.1003617

Abstract

Mechanistic and therapeutic insights in autoimmune diabetes would benefit from a more complete identification of relevant autoantigens. BDC2.5 TCR transgenic NOD mice express transgenes for TCR Vα1 and Vβ4 chains from the highly diabetogenic BDC2.5 CD4(+) T cell clone, which recognizes pancreatic β cell membrane Ags presented by NOD I-A(g7) MHC class II molecules. The antigenic epitope of BDC2.5 TCR is absent in β cells that do not express chromogranin A (ChgA) protein. However, characterization of the BDC2.5 epitope in ChgA has given inconclusive results. We have now identified a ChgA29-42 peptide within vasostatin-1, an N-terminal natural derivative of ChgA as the BDC2.5 TCR epitope. Having the necessary motif for binding to I-A(g7), it activates BDC2.5 T cells and induces an IFN-γ response. More importantly, adoptive transfer of naive BDC2.5 splenocytes activated with ChgA29-42 peptide transferred diabetes into NOD/SCID mice.