# Hybrid Peptides as Autoantigens for Diabetogenic CD4 T Cells

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $488,370

## Abstract

Abstract
This competing renewal application is to continue our studies on the role of hybrid insulin peptides (HIPs) as
neo-epitopes for autoreactive CD4 T cells in autoimmune diabetes. During this very productive period we
have established that HIPs formed from insulin C-peptide and other β-cell granule proteins are antigens for
large numbers of autoreactive CD4 T cells in the pancreas of NOD mice, can be used in strategies to
induce antigen-specific tolerance, and are also present in human islets and PBMC of patients with type 1
diabetes (T1D). Our objective in the next period of the award will be to characterize new insulin (Ins) B-
chain HIPs and T cells reactive to these HIPs, in both NOD mice and human subjects. We hypothesize that
antigenicity of the much studied insulin B chain peptide, B:9-23, is due to hybrid peptide formation between
sequences of B:9-23 and cleavage peptide products of other granule proteins. The rationale for pursuing
these studies is based on preliminary data indicating that B-chain HIPs containing B9-23 sequences are
strong agonists for insulin-reactive T cell clones and that T cells reactive to these HIPs can be identified in
the polyclonal T cell population of NOD mice. Our aims for this next project period are to (1) investigate the
role of B-chain HIP-reactive T cells in disease pathogenesis; (2) determine whether tolerance can be
induced with insulin B-chain HIPs coupled to biodegradable nanoparticles in NOD models of spontaneous
disease and islet transplantation; and (3) investigate the presence of B-chain HIP-reactive CD4 T cells in
human T1D and develop new human tetramers containing B-chain HIPs. The B-chain HIPs will provide
further tools for understanding the autoimmune response to pancreatic β-cell antigens in general, and
specifically the contribution of insulin-reactive T cells to the disease process. We predict that these studies
will lead to generation of reagents not only for tracking disease-relevant T cells, but also for developing and
expanding approaches to antigen-specific therapy.

## Key facts

- **NIH application ID:** 10911971
- **Project number:** 5R01DK081166-14
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** KATHRYN M HASKINS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $488,370
- **Award type:** 5
- **Project period:** 2011-04-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911971

## Citation

> US National Institutes of Health, RePORTER application 10911971, Hybrid Peptides as Autoantigens for Diabetogenic CD4 T Cells (5R01DK081166-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10911971. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*