# Role of molecular drivers in memory group 1 CD1-restricted T cell differentiation and Mycobacterium tuberculosis infection

> **NIH NIH F30** · NORTHWESTERN UNIVERSITY · 2021 · $44,288

## Abstract

Project Summary
Tuberculosis remains a serious global epidemic and with the rise of multi-drug resistant strains, an efficacious
vaccine solution is imperative. Synthetic subunit vaccines, which do not contain live bacteria, present
numerous advantages over attenuated vaccines by offering a safer option for immunocompromised individuals
and being amenable to rapid, scalable, and reproducible production. The subunit vaccines currently being
developed for Mycobacterium tuberculosis (Mtb) use peptide or protein antigens, which target MHC-restricted
conventional T cells, overlooking the potential of Mtb lipid antigens as vaccine candidates. Mycobacterial lipids
are presented by group 1 CD1 (CD1a, b, c) and group 2 CD1d to cognate T cells. Group 1 CD1-restricted T
cells can be identified in patients with TB and have been shown to contribute to protective immunity against
Mtb infection. In order to study further study group 1 CD1-restricted Mtb response, we previously created CD1
expressing transgenic mice (hCD1Tg) and CD1b-restricted T cell receptor transgenic T cells (DN1Tg) specific
for the dominant Mtb lipid antigen mycolic acid (MA). We have since showed that DN1 T cells can be activated
in vivo by vaccination with nanoparticles (NP) loaded with MA. We immunized hCD1Tg-DN1 mice with MA-NP
to generate memory DN1 T cells. Using transcriptome analysis, we then determined that memory DN1 T cells
most closely resemble T follicular helper (TFH) cells. In this proposal, we will assess whether two key TFH cell
molecules, Bcl6 and PD-1, are necessary for memory DN1 T cell differentiation. We will also validate findings
in the polyclonal setting using single cell sequencing. Finally, we will test whether memory DN1 T cell can
provide protection in Mtb infection conditions. Through this work, we will be able to understand unique
determinants of memory group 1 CD1-restricted T cells differentiation and their role in Mtb infection bringing us
a step closer to creating a lipid-based vaccine for Mtb.

## Key facts

- **NIH application ID:** 10146077
- **Project number:** 1F30AI157314-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Eva Morgun
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,288
- **Award type:** 1
- **Project period:** 2021-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146077

## Citation

> US National Institutes of Health, RePORTER application 10146077, Role of molecular drivers in memory group 1 CD1-restricted T cell differentiation and Mycobacterium tuberculosis infection (1F30AI157314-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146077. Licensed CC0.

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