# Human T cell responses permissive for progression to active TB disease

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $888,177

## Abstract

This project will identify antigen-specific human T cell signatures that allow progression to active TB disease, 
by prospectively collecting samples from high risk household TB contacts, and comparing M. tuberculosis 
antigen-specific T cell responses in those that subsequently progress to active TB and in those that do not. 
We will characterize the breadth (number of antigens) and specific patterns of antigen recognition by T cells, 
and we will determine the relationship between the subjects' T cell responses, their HLA allotypes, and their 
bacterial epitope sequences, to test two specific hypotheses: 1) that the ability of an individual's T cells to 
respond to M. tuberculosis epitopes is determined by the ability of that individual's HLA alleles to present the 
specific epitope sequences present in the bacteria that infected them; and 2) that the breadth and/or specific 
nature of antigen recognition is associated with the risk of progression to active TB. To provide more 
complete characterization of the molecular interactions between host and pathogen required for CD4 T cell 
responses, we will also characterize the diversity of T cell antigen receptors (TCRs) for selected epitopes, to 
test the hypothesis that subjects that progress to active TB have lower TCR diversity than do subjects that 
do not progress to active TB. In studies analogous to those in Project 1, we will use multiparameter mass 
cytometry to identify T cell phenotypes and/or functional responses characteristic of subsequent progression 
to active TB. The data from these studies will be used to synthesize T cell signatures associated with a 
lower or with a higher risk of progression to active TB; signatures associated with progression can be used to 
identify individuals at highest risk and prioritize them for preventive interventions, while low-risk signatures 
will guide TB vaccine development. We will also take advantage of our prospective study design to 
determine the extent to which latent TB infection (LTBI) protects against development of active TB after reexposure 
to an active TB case. Together, the proposed studies will provide unprecedented insight into the 
spectrum of antigen-specific T cell responses (T cell signatures) in humans infected with Mtb, and the 
association of specific T cell signatures with distinct outcomes.

## Key facts

- **NIH application ID:** 9989018
- **Project number:** 5U19AI111211-07
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Joel D. Ernst
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $888,177
- **Award type:** 5
- **Project period:** 2014-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989018

## Citation

> US National Institutes of Health, RePORTER application 9989018, Human T cell responses permissive for progression to active TB disease (5U19AI111211-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9989018. Licensed CC0.

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