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Review
. 2021 Apr 30:12:667870.
doi: 10.3389/fimmu.2021.667870. eCollection 2021.

Identifying New Hybrid Insulin Peptides (HIPs) in Type 1 Diabetes

Stuart I Mannering  1   2 , Alan F Rubin  3   4 , Ruike Wang  1 , Pushpak Bhattacharjee  1
Affiliations
Review

Identifying New Hybrid Insulin Peptides (HIPs) in Type 1 Diabetes

Stuart I Mannering et al. Front Immunol. .

Abstract

In 2016 Delong et al. discovered a new type of neoepitope formed by the fusion of two unrelated peptide fragments. Remarkably these neoepitopes, called hybrid insulin peptides, or HIPs, are recognized by pathogenic CD4+ T cells in the NOD mouse and human pancreatic islet-infiltrating T cells in people with type 1 diabetes. Current data implicates CD4+ T-cell responses to HIPs in the immune pathogenesis of human T1D. Because of their role in the immune pathogenesis of human T1D it is important to identify new HIPs that are recognized by CD4+ T cells in people at risk of, or with, T1D. A detailed knowledge of T1D-associated HIPs will allow HIPs to be used in assays to monitor changes in T cell mediated beta-cell autoimmunity. They will also provide new targets for antigen-specific therapies for T1D. However, because HIPs are formed by the fusion of two unrelated peptides there are an enormous number of potential HIPs which makes it technically challenging to identify them. Here we review the discovery of HIPs, how they form and discuss approaches to identifying new HIPs relevant to the immune pathogenesis of human type 1 diabetes.

Keywords: CD4+ T cell; autoimmunity; epitope; hybrid insulin peptides (HIPs); type 1 diabetes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Calculating the number of HIPs that could be generated from a 100 amino acid (AA) long protein. A hypothetical 100 amino acid long peptide is indicated by the red box. The first few of all possible 10 amino acid fragments, derived from this protein are shown in red. Potential HIPs, in both orientations of the composite fragments are shown. Assumptions made in calculating the number of potential HIPs that may form from a 100 amino acid protein are shown.
See this image and copyright information in PMC

References

    1. Mannering SI, Pathiraja V, Kay TW. The Case for an Autoimmune Aetiology of Type 1 Diabetes. Clin Exp Immunol (2016) 183(1):8–15. 10.1111/cei.12699 - DOI - PMC - PubMed
    1. Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, et al. . Demonstration of Islet-Autoreactive CD8 T Cells in Insulitic Lesions From Recent Onset and Long-Term Type 1 Diabetes Patients. J Exp Med (2012) 209(1):51–60. 10.1084/jem.20111187 - DOI - PMC - PubMed
    1. Noble JA. Immunogenetics of Type 1 Diabetes: A Comprehensive Review. J Autoimmun (2015) 64:101–12. 10.1016/j.jaut.2015.07.014 - DOI - PubMed
    1. Todd JA, Bell JI, McDevitt HO. Hla-DQ Beta Gene Contributes to Susceptibility and Resistance to Insulin-Dependent Diabetes Mellitus. Nature (1987) 329(6140):599–604. 10.1038/329599a0 - DOI - PubMed
    1. Nepom BS, Schwarz D, Palmer JP, Nepom GT. Transcomplementation of HLA Genes in IDDM. Hla-DQ Alpha- and Beta-Chains Produce Hybrid Molecules in DR3/4 Heterozygotes. Diabetes (1987) 36(1):114–7. 10.2337/diab.36.1.114 - DOI - PubMed

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