# Presentation of Qa-1 restricted peptides during homeostasis and viral infection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $49,720

## Abstract

Program Director/Principal Investigator (Robey, Ellen, A):
Abstract:
 Mouse Qa-1 is a member of the conserved MHC-E family of non-classical MHC-1 molecules (MHC1b). In
most cells, MHC-E presents peptides derived from the leader sequences of classical (MHC1a) molecules, and
regulates the function of NK cells through the receptors NKG2A and NKG2C. MHC-E molecules can also
present self and pathogen derived peptides to CD8 T cells. The signals that lead to presentation of alternative
peptides by MHC-E, and the functions of the responding CD8 T cells remain poorly understood. Recently,
studies of a highly effective HIV vaccine based on a CMV vector revealed a prominent MHC-E restricted CD8
T cell response, raising new interest in understanding the presentation mechanisms and in vivo functions of
MHC-E.
 Together with our collaborators, we have been investigating a Qa-1-restricted T cell response to cells
lacking the ER aminopeptidase associated with antigen processing (ERAAP ko) {Nagarajan:2012cn}. The
responding CD8 T cells recognize a 9-mer peptide derived from a self-protein (FL9 from FAM49B) presented
by Qa-1(b) (called QFL T cells). QFL T cells use a semi-invariant TCR alpha chain, and have characteristics of
both conventional and non-conventional CD8 T cells. Our preliminary data indicate that QFL T cells encounter
high affinity Qa-1 restricted ligands at steady state and during viral infection. We propose to use a newly
generated TCR transgenic mouse strain to probe the in vivo generation of Qa-1 restricted ligands for QFL T
cells in both steady state and during viral infection. In Aim 1, we will identify the pMHC ligands involved in
positive and agonist selection of QFL T cells, and will identify the thymic cell types that present the ligands. In
Aim 2, we will identify the ligand(s) that drive the homeostatic expansion of QFL T cells, and will determine
when, in what tissue, and by what cell type(s) they are presented. In Aim 3, we will determine the mechanisms
that lead to priming of QFL T cells during MCMV infection, and will test whether QFL T cells induced during
MCMV infection can kill infected cells and provide immune protection.
 Our results will shed new light on how MHC-E presentation regulates T cell responses, with important
implications for vaccine design.
OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

## Key facts

- **NIH application ID:** 10379603
- **Project number:** 3R01AI149341-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** LAURENT COSCOY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $49,720
- **Award type:** 3
- **Project period:** 2021-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379603

## Citation

> US National Institutes of Health, RePORTER application 10379603, Presentation of Qa-1 restricted peptides during homeostasis and viral infection (3R01AI149341-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10379603. Licensed CC0.

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