Back to Search Start Over

A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery

Authors :
Derek M Woodruff
Elizabeth Motunrayo Kolawole
Baoyu Liu
Brian D. Evavold
Jennifer D. Hood
Dario A. A. Vignali
Maria Bettini
Source :
Diabetes
Publication Year :
2020
Publisher :
American Diabetes Association, 2020.

Abstract

β-Cell antigen recognition by autoreactive T cells is essential in type 1 diabetes (T1D) pathogenesis. Recently, insulin hybrid peptides (HIPs) were identified as strong agonists for CD4 diabetogenic T cells. Here, using BDC2.5 transgenic and NOD mice, we investigated T-cell recognition of the HIP2.5 epitope, which is a fusion of insulin C-peptide and chromogranin A (ChgA) fragments, and compared it with the WE14 and ChgA29–42 epitopes. We measured in situ two-dimensional affinity on individual live T cells from thymus, spleen, pancreatic lymph nodes, and islets before and after diabetes. Although preselection BDC2.5 thymocytes possess higher affinity than splenic BDC2.5 T cells for all three epitopes, peripheral splenic T cells maintained high affinity only to the HIP2.5 epitope. In polyclonal NOD mice, a high frequency (∼40%) of HIP2.5-specific islet T cells were identified at both prediabetic and diabetic stages comprising two distinct high- and low-affinity populations that differed in affinity by 100-fold. This high frequency of high- and low-affinity HIP2.5 T cells in the islets potentially represents a major risk factor in diabetes pathogenesis.

Details

ISSN :
1939327X and 00121797
Volume :
69
Database :
OpenAIRE
Journal :
Diabetes
Accession number :
edsair.doi.dedup.....7f34c9b76aff1e5ca2e4b30a119c2bfc
Full Text :
https://doi.org/10.2337/db19-0399