| First Author | Liu B | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 3 | Pages | 381-391 |
| PubMed ID | 31806623 | Mgi Jnum | J:285351 |
| Mgi Id | MGI:6392419 | Doi | 10.2337/db19-0399 |
| Citation | Liu B, et al. (2020) A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery. Diabetes 69(3):381-391 |
| abstractText | beta-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 ( approximately 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. |
