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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $574,805

## 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 germ-line encoded receptor CD94/NKG2. 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 et al., 2012). The
responding CD8 T cells recognize a 9-mer peptide derived from a self-protein (FL9 from FAM49) presented by
Qa-1(b) (called QFL T cells). QFL T cells use an invariant TCR a, 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:** 10814294
- **Project number:** 5R01AI149341-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** LAURENT COSCOY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $574,805
- **Award type:** 5
- **Project period:** 2020-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10814294

## Citation

> US National Institutes of Health, RePORTER application 10814294, Presentation of Qa-1 restricted peptides during homeostasis and viral infection (5R01AI149341-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10814294. Licensed CC0.

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