# Identification of relevant peptides involved in the initiation and progression of autoimmune diabetes

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $434,834

## Abstract

Project Summary
We propose a collaborative project involving immunologists experienced in autoimmune
diabetes, mass-spectrometrists, and endocrinologists-diabetologists. Our combined efforts are
to specifically identify relevant peptides from beta cell proteins involved in the
immunopathogenesis of type 1 diabetes. The project combines experimental studies in
diabetes-prone mice that should lead to targeted evaluation of human samples. The ultimate
goal is to identify peptides that form the substrate for the autoreactive MHC-II response that
initiates and perpetuates the process. Important is to identify relevant diabetogenic antigens at
different stages of the autoimmune reaction from pre-diabetes to the initial progression: it will
include their characterization, source in beta cells, involvement in the disease process, and sites
of presentation.
Aim 1 consists of an identification of novel peptides derived from beta cell granules of
both mice and humans. We examine vesicles isolated from beta cells with a major focus on
crinosomes. Crinosomes and insulin dense core granules will be isolated during different stages
of diabetes development, their peptides will be isolated and examined by sophisticated mass
spectrometry with state of the art instrumentation and technology. We will place emphasis in
unique structural or post translational changes in peptides and whether the panoply of them
changes as the beta cell progresses into active diabetes. We also will examine vesicles and
exocytosed products from human islets from recently diseased individuals.
Aim 2 will be an immunological validation of novel peptides identified by mass
spectrometry. Immunological and biochemical assays will be used to validate the ability of beta
cell derived peptides to bind to I-Ag7 and activate T cells in vitro and in vivo.
Aim 3 will be the Identification and validation of the MHC-II-bound peptidome in islets and
secondary lymphoid organs. We plan to examine the peptidome eluted from MHC-II
molecules expressed by phagocytes obtained from islets, peripheral lymph nodes, and spleens
of the NOD mouse and to characterize/validate them as in Aims 1/2. This is the seminal test to
prove an immunogenic peptide, that is, it's a positive identification bound in vivo to MHC-II
alleles.

## Key facts

- **NIH application ID:** 10246429
- **Project number:** 5R01DK120340-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** EMIL Raphael UNANUE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $434,834
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246429

## Citation

> US National Institutes of Health, RePORTER application 10246429, Identification of relevant peptides involved in the initiation and progression of autoimmune diabetes (5R01DK120340-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246429. Licensed CC0.

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