# T cell repertoire for hybrid insulin peptides

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $492,710

## Abstract

Project Abstract
Identification of the autoantigens that drive the pathogenic T cell response in type 1 diabetes (T1D) is a
research goal of great importance because of the implications for biomarker discovery and disease
prevention strategies. Our lab has focused on the role of CD4 T cells in both pathogenesis and regulation
of disease with particular emphasis on their target antigens. Using a proteomic approach and the BDC
panel of CD4 T cell clones as our antigen detection system, we recently discovered that the peptide ligands
that activate several clones in our panel, including the prototype clone BDC-2.5, were formed through a
novel post-translational modification involving formation of hybrid peptides between peptide cleavage
products of -cell proteins such as ChgA or IAPP and sequences from insulin C-peptide. The discovery of
hybrid insulin peptides (HIPs) as a new class of neoantigens raises questions as to the extent of HIP
reactivity in T1D and whether T cells reactive to HIPs drive the autoimmune process. We hypothesize that
HIP-reactive T cells can serve as biomarkers of disease and that the discovery of new HIP reactivities in
NOD mice and patients with T1D will offer new possibilities to stage the disease before it occurs. To test
this hypothesis, we propose to (1) investigate the T cell repertoire for hybrid insulin peptides (HIPs) in the
NOD mouse; (2) discover C-peptide HIP reactivities using combinatorial peptide pools in T1D and at risk
subjects and (3) monitor phenotype and TCR of HIP-reactive T cells over time in subjects at risk for T1D.

## Key facts

- **NIH application ID:** 10170349
- **Project number:** 5R01DK122566-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** KATHRYN M HASKINS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $492,710
- **Award type:** 5
- **Project period:** 2019-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170349

## Citation

> US National Institutes of Health, RePORTER application 10170349, T cell repertoire for hybrid insulin peptides (5R01DK122566-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10170349. Licensed CC0.

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