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

Stuart I Mannering,Ruike Wang,Alan F Rubin,Pushpak Bhattacharjee

doi:10.3389/fimmu.2021.667870

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.

Highlights

Type 1 diabetes (T1D) is an autoimmune disease caused the T-cell mediated destruction of the pancreatic beta cells [1]
Solving the mystery of the ligand for BDC-2.5 was interesting, but it was not clear if hybrid insulin peptides (HIPs) specific CD4+ T cells arose in people with T1D and if they played any role the pathogenesis of T1D. We addressed this question by testing a panel of 16 putative human HIPs, designed based on the HIPs identified in the NOD mouse, against of human islet-infiltrating CD4+ T-cell clones
From these experiments we identified two clones that responded to a Cpeptide-IAPP2 HIP [12]

Summary

Introduction

Type 1 diabetes (T1D) is an autoimmune disease caused the T-cell mediated destruction of the pancreatic beta cells [1]. Human islet-infiltrating CD4+ T cells recognize several epitopes derived from the C-peptide presented by HLA-DQ8, or DQ8trans [11]. A hybrid insulin peptide, or HIP, is a CD4+ T-cell epitope that is formed by the posttranslational fusion of two peptide fragments [reviewed by [13]].

Results

Conclusion