# Dual TCR Expression Effects on Alloreactivity and Transplantation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $382,057

## Abstract

Project Summary/Abstract
In normal physiology, the repertoire of human T cells includes a 10% subpopulation that expresses two, rather
than a single, T cell receptor (TCR). Despite the obvious implications of dual-specificity at the clonal level, the
function of this dual TCR subpopulation remains largely unknown. We recently proposed the novel paradigm
and provided evidence demonstrating that naturally-arising dual TCR expression is important in thymopoiesis
and that dual TCR cells have exceptional ability to recognize ligands driving alloreactivity and autoreactivity. This
reactivity is relevant to disease, as we demonstrated in mouse models and human patients that dual TCR T cells
are important drivers in graft versus host disease, a severe and life-threatening T cell-mediated complication of
hematopoietic stem cell transplantation. Data from other models also link dual TCR T cells to autoimmune
disease such as diabetes. Despite evidence of the importance of dual TCR cells, they have been understudied
due to the inability to definitively identify, isolate, and functionally study T cells expressing dual TCRs. To address
this, we have developed novel approaches including single-cell TCR sequencing of mouse and human cells, and
transgenic mice with fluorescent reporters for TCRα. We intend that these tools will enable us to address our
hypotheses and generate novel insights into fundamental TCR biology to identify potential avenues to improve
clinical transplantation.

## Key facts

- **NIH application ID:** 10356146
- **Project number:** 5R01AI151293-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Gerald Patrick Morris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $382,057
- **Award type:** 5
- **Project period:** 2020-03-05 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10356146

## Citation

> US National Institutes of Health, RePORTER application 10356146, Dual TCR Expression Effects on Alloreactivity and Transplantation (5R01AI151293-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10356146. Licensed CC0.

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