# Identification of human Mtb-specific T cell signatures that are associated

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $378,442

## Abstract

Identifying immune correlates of control and protection to Mycobacterium tuberculosis (Mtb) infection is 
essential for designing vaccines for TB. The overall goals of our TBRU application are to identify 
antigen-specific T cell responses that are associated with distinct outcomes of Mtb infection: clearance, 
persistence, and progression to active disease. We currently lack the knowledge or tools to distinguish 
individuals who harbor persistent Mtb infection from those who may have resolved infection via 
immune-mediated clearance of bacteria. In Project 1 we will focus on "Identification of human Mtb-specific T 
cell signatures that are associated with resolved and persistent Mtb infection". We will test the hypothesis 
that distinct Mtb-specific memory T cell profiles are associated with bacterial clearance or persistence. This 
is supported by our data showing that distinct antigen-specific memory T cell phenotypes and functions are 
associated with LTBI, active TB disease and clinically resolved TB. We propose to use 
chemotherapy-mediated clearance to model immune-mediated clearance of Mtb, as the treatment regimen 
for LTBI should result in significant reduction or elimination of bacteria. We will enroll individuals with LTBI in 
a low-exposure setting (Atlanta, GA) and systematically compare their antigen-specific T cell responses 
before and after treatment. We will delineate the spectrum of antigens recognized by Mtb-specific memory 
CD4 and CD8 T cells, characterize their memory phenotypes, functional capacities and transcriptional 
profiles (Aim 1). Using statistical analyses, we will derive Mtb-specific T cell signatures that represent 
bacterial clearance and persistence and evaluate these (with Project 3), in non-human primates (NHP) and 
determine the prevalence of these signatures in treatment-naive individuals with LTBI in Kenya (Aim 2). We 
will longitudinally assess the dynamics of Mtb-specific memory T cell responses and their homeostatic 
turnover in LTBI (Aim3). We will also compare clearance/persistence signatures with those associated with 
progression to TB (with Project 2). Overall, these studies will provide insights into protective immunity to TB 
and new tools to evaluate Mtb persistence or clearance in LTBI.

## Key facts

- **NIH application ID:** 9989013
- **Project number:** 5U19AI111211-07
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jyothi Rengarajan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,442
- **Award type:** 5
- **Project period:** 2014-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989013

## Citation

> US National Institutes of Health, RePORTER application 9989013, Identification of human Mtb-specific T cell signatures that are associated (5U19AI111211-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989013. Licensed CC0.

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