# CD1 Presentation of Self Lipids to Human T Cells

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $493,237

## Abstract

Project Summary - CD1 Presentation of Self Lipids to Human T cells – D. Branch Moody
T cells play a central role in the pathogenesis of human autoimmune diseases, including allergy and drug
hypersensitivity syndromes. For decades studies of T cell autoantigens have emphasized peptide
antigens bound to MHC proteins. This proposal investigates the basis by which self lipid antigens bind to
human CD1 antigen presenting molecules, leading to autoreactive T cell responses. This competing
renewal builds on an existing program of development that has invented human CD1a and CD1b
tetramers and used them to discover previously unknown lipid autoantigens for T cells, including
squalene and phosphatidylglycerol. To provide a general basis for lipid epitope mapping, we will use
mass spectrometry to broadly identify many hundreds of self lipids that bind to CD1 proteins in human
cells. Using tetramers, we will identify and clone autoreactive T cell receptors and measure their binding
to CD1-self lipid complexes. Building on recently published studies showing that CD1a autoreactive T
cells are increased in patients with allergy syndromes, we will measure CD1a-reactive T cell responses in
human cohorts. Finally, we will investigate a new mechanism by which CD1a proteins present common
skin irritants from clinical patch tests to T cells, bypassing mechanisms that relate to peptide
haptenization. Overall, these studies will extend the spectrum of natural T cell autoantigens to include
self lipids and investigate their roles in common allergic diseases.

## Key facts

- **NIH application ID:** 10187522
- **Project number:** 5R01AR048632-20
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** DAVID Branch MOODY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $493,237
- **Award type:** 5
- **Project period:** 2002-09-20 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187522

## Citation

> US National Institutes of Health, RePORTER application 10187522, CD1 Presentation of Self Lipids to Human T Cells (5R01AR048632-20). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10187522. Licensed CC0.

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