Characterization of Human CD4 T Cells Specific for a C-Peptide/C-Peptide Hybrid Insulin Peptide.

Frontiers in Immunology
Timothy A WilesRocky L Baker

Abstract

Hybrid Insulin Peptides (HIPs), which consist of insulin fragments fused to other peptides from β-cell secretory granule proteins, are CD4 T cell autoantigens in type 1 diabetes (T1D). We have studied HIPs and HIP-reactive CD4 T cells extensively in the context of the non-obese diabetic (NOD) mouse model of autoimmune diabetes and have shown that CD4 T cells specific for HIPs are major contributors to disease pathogenesis. Additionally, in the human context, HIP-reactive CD4 T cells can be found in the islets and peripheral blood of T1D patients. Here, we performed an in-depth characterization of the CD4 T cell response to a C-peptide/C-peptide HIP (HIP11) in human T1D. We identified the TCR expressed by the previously-reported HIP11-reactive CD4 T cell clone E2, which was isolated from the peripheral blood of a T1D patient, and determined that it recognizes HIP11 in the context of HLA-DQ2. We also identified a HIP11-specific TCR directly in the islets of a T1D donor and demonstrated that this TCR recognizes a different minimal epitope of HIP11 presented by HLA-DQ8. We generated and tested an HLA-DQ2 tetramer loaded with HIP11 that will enable direct ex vivo interrogation of CD4 T cell responses to HIP11 in human patients and c...Continue Reading

References

Jul 26, 2002·Genes and Immunity·F Pociot, M F McDermott
Mar 25, 2006·Nature Reviews. Immunology·E Yvonne JonesChristian Siebold
Mar 6, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gerald T Nepom
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May 26, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathaniel J SchuldtBryce A Binstadt
Dec 27, 2018·Journal of Proteome Research·T. Aaron WilesThomas Delong
Jun 9, 2019·Diabetes·Rocky L BakerThomas Delong
Apr 16, 2020·Diabetes·David Arribas-LaytonEddie A James

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