# Calcium Signaling in MR1-Dependent Antigen Presentation

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $192,500

## Abstract

Project Summary
The fundamental role of the immune system is to detect self from non-self. The detection and elimination of
microbial infection is critical for human survival. One challenge to the immune system is infection from an
intracellular microbe because the microbe masks its presence in a host cell. One strategy of the immune
system to detect microbes is the sampling of different kinds of antigens, such as peptides, lipids and
glycolipids, by antigen presenting molecules. A fundamentally unique arm of the immune system is MR1, which
is an antigen presenting molecule that is intracellular, ubiquitously expressed across tissues, and detects small
molecules derived from microbial metabolism. These features suggest that MR1 is poised to detect intracellular
microbes. MR1 presents antigens to MR1-restricted T cells. These T cells are highly prevalent in the lungs and
have the ability to kill infected cells. Because MR1 presents small molecule antigens and adopts an
intracellular distribution, the mechanisms governing MR1 sampling of the intracellular environment are distinct
from other antigen presenting molecules. These mechanisms remain unknown. Our hypothesis is that
intracellular calcium signaling is important for MR1 antigen presentation because MR1 resides in vesicles and
endosomal vesicles are a source of intracellular calcium. We use Mycobacterium tuberculosis (Mtb) as a
model for intracellular infection and have identified calcium-sensitive trafficking proteins and calcium channels
important for MR1 antigen presentation. Aim 1 of this study will determine the relative contribution of specific
calcium-sensitive Synaptotagmins to MR1 antigen presentation and we will use live-cell imaging and
fluorescently tagged constructs to determine how these calcium sensitive Synaptotagmins interact with MR1
and Mtb. Aim 2 of this study will determine the relative contribution of Two-pore channels (calcium channels) to
MR1 antigen presentation, interactions of these channels with MR1 and with Mtb, and we will generate an MR1
construct with a genetically encoded calcium indicator, which may allow us to determine the compartment
where MR1 is loaded with antigens from Mtb.

## Key facts

- **NIH application ID:** 10086964
- **Project number:** 5R21AI151079-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Elham Karamooz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2020-01-21 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086964

## Citation

> US National Institutes of Health, RePORTER application 10086964, Calcium Signaling in MR1-Dependent Antigen Presentation (5R21AI151079-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10086964. Licensed CC0.

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