# Mechanisms of MHCII expression and CD4+ T cell activation during Chlamydia trachomatis infection

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2021 · $230,884

## Abstract

Project Summary
The mammalian host requires CD4+ T cells to survive infections with many distinct intracellular pathogens.
Loss of CD4+ T cells leads to susceptibility to infections caused by Chlamydia trachomatis, Mycobacterium
tuberculosis and others. Antigen presenting cells (APCs) are at the interface of invading pathogens and
adaptive immunity, sensing the infected environment and signaling directly to CD4+ T cells. The expression of
Major Histocompatibility Complex II (MHCII) on APCs is critical for CD4+ T cells to detect their cognate
antigens and activate an appropriate host response. Many pathogens manipulate the expression of MHCII to
evade protective immunity. While complete loss of MHCII prevents CD4+ T cell function, how modulation of
MHCII levels during infection impacts the effectiveness of pathogen-specific CD4+ T cell responses remains
unknown. We hypothesize that MHCII expression levels are an important factor in the activation and effector
function of antigen-specific CD4+ T cells. By understanding how MHCII is regulated at a global scale we will be
positioned to develop interventions that modulate MHCII expression in order to overcome pathogen virulence
strategies aimed at blunting protective host responses. We performed a genome-wide CRISPR-Cas9 screen to
identify regulators of MHCII surface expression in activated APCs. We found over 200 genes that significantly
alter surface MHCII expression with no described function in MHCII regulation. Here, using CRISPR-Cas9
mediated gain-of-function and loss-of-function approaches we will systemically identify priority candidates that
enhance or inhibit MHCII surface expression and begin to dissect their mechanisms of MHCII control. We will
next determine how modulation of MHCII expression directly alters the pathogen-specific CD4+ T cell response
during genital infections with Chlamydia muridarum. We are investigating Chlamydia because it is an important
pathogen clinically as the number one bacterial sexually transmitted infection in the United States. Chlamydia
causes severe pathologies that lead to infertility, ectopic pregnancy and pelvic inflammatory disease. We will
track the Chlamydia-specific CD4+ T cell response using immunological tools that do not exist for most
pathogens. In combination with our CRISPR approaches we are uniquely positioned to directly examine how
MHCII expression impacts the Chlamydia-specific CD4+ T cell response ex vivo and in vivo. We will determine
how enhanced or reduced MHCII expression on APCs alters a range of CD4+ T cell phenotypes including
activation, proliferation, effector function, protection and the development of genital tract pathologies. Our
focused studies on the role of MHCII expression during C. trachomatis infection will broadly identify regulators
of MHCII that can then be explored in a range of disease states where CD4+ T cell activation is required and
MHCII is manipulated including other intracellular pathogens or cancers.

## Key facts

- **NIH application ID:** 10086392
- **Project number:** 5R21AI146504-02
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Andrew Olive
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $230,884
- **Award type:** 5
- **Project period:** 2020-01-17 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086392

## Citation

> US National Institutes of Health, RePORTER application 10086392, Mechanisms of MHCII expression and CD4+ T cell activation during Chlamydia trachomatis infection (5R21AI146504-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10086392. Licensed CC0.

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