# Identify the host genetic determinants of immune response and TB countrol

> **NIH NIH U19** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $505,084

## Abstract

T cells play a critical role in the host response to Mtb infection, and are their antigen specificity forms the 
basis of widely used clinical immunodiagnostic tests. MHC-restricted effector memory T cells protect the host 
from progression to active TB disease, but the particular effector functions, which mediate control are 
unknown. In a well characterized human patient cohort in Lima, Peru, we will determine the association of 
active TB disease with 400 transcripts measured in highly purified effector memory T cells. Transcripts 
associated with lack of disease progression will be validated by PCR and protein measurements to define 
gene products that can be measured as surrogates for protection from TB progression and targets for 
immunotherapy development. Nearly all current technology development efforts related to adjuvant 
formulation, vaccine design and immunodiagnosis focus on MHC antigen presenting molecules. However, 
recent studies show that non-classical CDIb and MRI proteins present mycobacterial lipids and metabolites 
to T cells in TB disease. Emphasizing new ex vivo methods and CD1 tetramers, we will measure the 
relationship of expansion of lipid- and metabolite-specific GEM T cells and MAIT cells during human and 
guinea pig infection and relapse. In particular, we propose to (a) measure GEM T cell expansion ex vivo 
during acute human tuberculosis infection (b) comparative nanostring profiling of effector functions of MAIT 
cells and GEM T cells, and (c) detect CDIb-restricted T cells in guinea pigs using CDIb tetramers. These 
translational studies seek to establish the first tractable small animal model of in vivo CDIb function and 
detect a causal relationship of infection with invariant T cell activation. Bypassing the genetic complexities of 
human MHC proteins, activation of invariant T cells by lipids and metabolites offers potentially more uniform 
outcomes that could be detected or modulated with lipids and vitamin metabolites (Project 4).

## Key facts

- **NIH application ID:** 9857534
- **Project number:** 5U19AI111224-06
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** MEGAN B MURRAY
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $505,084
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857534

## Citation

> US National Institutes of Health, RePORTER application 9857534, Identify the host genetic determinants of immune response and TB countrol (5U19AI111224-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9857534. Licensed CC0.

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