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A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery
- 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.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
T-Lymphocytes
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Antibody Affinity
Receptors, Antigen, T-Cell
Epitopes, T-Lymphocyte
Mice, Transgenic
030209 endocrinology & metabolism
Spleen
Thymus Gland
Epitope
Islets of Langerhans
Mice
03 medical and health sciences
0302 clinical medicine
Antigen
Mice, Inbred NOD
Internal Medicine
medicine
Animals
NOD mice
Type 1 diabetes
Thymocytes
C-Peptide
biology
Chemistry
Insulin
Chromogranin A
medicine.disease
Molecular biology
Peptide Fragments
Diabetes Mellitus, Type 1
030104 developmental biology
medicine.anatomical_structure
Polyclonal antibodies
biology.protein
Lymph Nodes
Immunology and Transplantation
Subjects
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