# Investigating the role of gamma delta (γδ) T cells in the control of Mycobacterium tuberculosis infection

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $48,974

## Abstract

SUMMARY
Mycobacterium tuberculosis (Mtb) is the pathogenic bacteria which causes tuberculosis (TB) disease and was
responsible for 1.6 million deaths worldwide in 2021. It is well-established through human and animal studies
that alpha-beta (αβ) T cells are important for the control of Mtb infection, but the role of gamma-delta (γδ) T cells
is less well-defined. γδ T cells express T cell receptor (TCR) heterodimers comprised of a γ-chain and δ-chain
that mediate recognition of a variety of lipids or small molecules presented by major histocompatibility-like
ligands, such as cluster of differentiation 1 (CD1) or butyrophilin molecules. There is growing evidence that γδ T
cells are important in the early protective immune response against Mtb in the lung. The central hypothesis of
this application is that γδ T cells contribute to control of Mtb infection through recognition of mycobacterial lipids
and promotion of an enhanced adaptive immune response. A subset of γδ T cells, termed Vδ1 cells, are enriched
in tissue and have known reactivity to mycobacterial lipids presented by CD1 molecules. In AIM 1 we will evaluate
the molecular mechanisms underlying Vδ1 T cell lipid antigen recognition through analysis of in vitro expanded
clones and computational analysis of lipid-specific Vδ1 TCR motifs. By investigating specific TCR motifs
governing recognition of mycobacterial lipids by Vδ1 T cells, we will determine shared TCR characteristics that
will enable their identification in clinical cohorts. A major challenge to the field has been the lack of a suitable
animal model to understand the role of γδ T cells in mediating protective immunity to Mtb. We will develop a
novel in vitro granuloma model using the palatine tonsil, a readily accessible human mucosal tissue, and
investigate the role of γδ T cells in mechanisms of bacterial control. Our preliminary data reveal that the tonsil
contains γδ T cell subsets which respond to in vitro mycobacterial infection and specialized dendritic cells subsets
that can prime T cell responses. Thus, in AIM 2 we will use tonsil cells to study γδ T cell interactions with dendritic
cells in response to mycobacterial infection and develop an in vitro granuloma model and investigate the role of
γδ T cells in granuloma organization. A tractable tonsil-based in vitro granuloma system will be an important
contribution to the field and provides a unique system to interrogate the function of γδ T cells in response to Mtb.
Together, our proposal will lead to increased understanding of γδ T cells and profile their involvement in the
protective immune response to mycobacteria.

## Key facts

- **NIH application ID:** 10994023
- **Project number:** 1F31AI186325-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Victoria Tappen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994023

## Citation

> US National Institutes of Health, RePORTER application 10994023, Investigating the role of gamma delta (γδ) T cells in the control of Mycobacterium tuberculosis infection (1F31AI186325-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10994023. Licensed CC0.

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