Diabetogenic T-cell clones recognize an altered peptide of chromogranin A.

Abstract:

: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.

journal_name

Diabetes

journal_title

Diabetes

authors

Delong T,Baker RL,He J,Barbour G,Bradley B,Haskins K

doi

10.2337/db12-0112

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

3239-46

issue

12

eissn

0012-1797

issn

1939-327X

pii

db12-0112

journal_volume

61

pub_type

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