# Responses to Hybrid Insulin Peptides as Biomarkers of Disease Activity in Human Type 1 Diabetes

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $388,750

## Abstract

Abstract: T Cell Responses to Hybrid Insulin Peptides as Biomarkers of Disease Activity in
Type 1 Diabetes
An important objective in T1D research is the investigation of autoantigens that activate effector T cells
and trigger the inflammatory process in islet beta-cells. We recently identified Hybrid Insulin Peptides
(HIPs) as a new class of autoantigens in type 1 diabetes (T1D). These neoantigens are created by the
fusion of insulin fragments with peptides from other secretory granule proteins such as chromogranin
A (ChgA), islet amyloid polypeptide (IAPP), neuropeptide Y (NPY) or insulin itself. Because insulin is
present only in pancreatic beta cells, this discovery might provide an explanation for organ-specific
autoimmunity in T1D. Importantly, CD4 T cells responding to HIPs have been isolated from the islets
of deceased T1D patients, demonstrating the relevance of these autoantigens to the human disease.
We hypothesize that T cells reactive to HIPs can serve as biomarkers of disease. Our goals in this
project are (1) to characterize T cell responses to HIPs in the PBMCs of T1D and controls; (2) to
determine the extent of reactivity to insulin B:9-23 Hybrid Insulin Peptides in recent onset T1D patients;
(3) Investigate the presence and phenotype of HIP-reactive T cells in the natural history of T1D.

## Key facts

- **NIH application ID:** 10177861
- **Project number:** 5R01AI146202-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Rocky Lee Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 5
- **Project period:** 2020-06-02 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10177861

## Citation

> US National Institutes of Health, RePORTER application 10177861, Responses to Hybrid Insulin Peptides as Biomarkers of Disease Activity in Human Type 1 Diabetes (5R01AI146202-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10177861. Licensed CC0.

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