# Exploiting the Mechanobiology of PD-1 for Cancer Immunotherapy

> **NIH NIH U01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2021 · $75,971

## Abstract

Project Summary
Alopecia Areata (AA) is an autoimmune disease affecting ~2% of the world population, especially affecting
black women disproportionately, with no cure at the present time. It manifests as inflammatory response of the
hair follicles where immune cells, cytotoxic T cells in particular, attack self-tissue, resulting in hair loss. The
mechanism underlying this autoimmune reaction is incomplete understood, and the disease-driving antigens
recognized by the specific T-cell receptors (TCR) are not known. The objectives of this project are to identify
and characterize Alopecia Areata-specific and force sensitive antigen and cognate TCRs. It is widely accepted
that the disease is induced by a loss of immune privilege in hair follicles, leading to the loss of immune
tolerance of a subpopulation of CD8+ T cells that recognize self-antigens. We hypothesize that the self-antigen
peptide-histocompatibility complex (pMHC) interaction with TCR is stronger than those that provide tonic
signals for T cell survival but weaker than the pathogenic-pMHC-TCR interactions. The two specific aims are:
1) To identify AA-driving antigens and their cognate TCRs in human and mouse using a newly developed
pMHC-tetramer library-stained single-cell sequencing technique.
2) To characterize the force-dependent AA-pMHC-TCR interaction and compare it with self- and pathogenic-
pMHC-TCR interactions using the biomembrane force probe technology of the Zhu lab.
Completing these aims will pave the way for future studies investigating TCR signaling induced by pMHC, the
resulting T-cell activation/function, improved transgenic TCR mouse models for AA, and an eventual cure.

## Key facts

- **NIH application ID:** 10381102
- **Project number:** 3U01CA250040-02S1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Rafi Ahmed
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,971
- **Award type:** 3
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381102

## Citation

> US National Institutes of Health, RePORTER application 10381102, Exploiting the Mechanobiology of PD-1 for Cancer Immunotherapy (3U01CA250040-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10381102. Licensed CC0.

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