# Multiple Autoantigens, Multiple Epitopes of Type 1 Diabetes

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

## Abstract

Project Summary
The overarching goal of our research is to develop new biomarkers of islet autoimmunity and to translate these
discoveries to the prevention of human type 1 diabetes (T1D). During the last funding period, we developed a
multiplexed assay to detect serum autoantibodies to islet and non-islet autoantigens with excellent sensitivity
and predictive value when compared to our traditional radio-binding assays. The proposed studies will broaden
the spectrum of relevant autoantigens to those that are post-translationally modified (PTM) as well as provide
insights into when native versus PTM binding autoantibodies develop in the natural history of T1D. Our recent
findings have strengthened the evidence for autoreactive T cells responding to (pro)insulin, including those
activated by hybrid insulin peptides (HIPs) and defective ribosomal insulin products (DRiPs), within the residual
pancreatic islets of T1D organ donors. However, we still lack robust T cell biomarkers that could reflect the
activity of autoreactive T cells, especially at the earliest stages of islet autoimmunity or during immunomodulation
to prevent progression to clinical diabetes. Assays for islet autoantibodies and autoreactive T cells that measure
both natural and modified islet autoantigens, combined with a better understanding of their relationship, will
enhance our knowledge of T1D pathogenesis and improve prediction of progression through the stages of T1D.
In specific aim 1, we will optimize and multiplex autoantibody assays to native and PTM modified islet
autoantigens to determine the temporal development of these antibodies in longitudinal samples from children
prospectively followed from birth to development of islet autoimmunity and clinical diabetes. Specific aim 2
focuses on developing a non-cellular T cell biomarker of islet autoimmunity measured from whole blood DNA
using the T cell receptor sequences obtained from residual islets of T1D organ donors. The successful
completion of this proposal will result in scalable assays for the measurement of islet autoantibodies and
autoreactive T cells, and improved understanding regarding the timing of autoantibody and T cell immune
responses to native and post-translationally modified islet autoantigens during the development of T1D.

## Key facts

- **NIH application ID:** 10209068
- **Project number:** 2R01DK032083-37
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** AARON W MICHELS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,750
- **Award type:** 2
- **Project period:** 1982-07-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209068

## Citation

> US National Institutes of Health, RePORTER application 10209068, Multiple Autoantigens, Multiple Epitopes of Type 1 Diabetes (2R01DK032083-37). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10209068. Licensed CC0.

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