# Modulation of CD8+ T Cell Responses by HLA-F

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $195,000

## Abstract

CD8+ T cells are critical for clearance of viral-infected cells and tumor cells. They recognize antigens presented
by human leukocyte antigen class I (HLA-I) molecules. HLA-F is a non-classical HLA-I molecule that has
recently been drawing a lot of attention due to its potential significance in several viral infections and cancers.
Although HLA-F was previously believed to be expressed only as open conformers (without peptide), recent
studies showed that HLA-F can also be expressed as peptide-associated form. Due to its limited
polymorphisms, HLA-F is an attractive target for viral infection control and cancer immunotherapy. However, it
is still not clear whether and how HLA-F modulates the function of CD8+ T cells.
In this proposal, we expect to address the function of HLA-F in CD8+ T cell responses with the following
specific aims: Aim 1: Determine the HLA-F antigen presentation pathway. Both of the accumulation in the
endoplasmic reticulum (ER) and the open conformation on the cell surface indicate peptide loading of HLA-F in
the ER is inefficient. Our preliminary study suggests an unconventional antigen presentation pathway. We will
determine where and how peptides are loaded to HLA-F, which will facilitate the future vaccine design. Aim 2:
Determine the effect of HLA-F on CD8+ T cell activation. HLA-F specific CD8+ T cells will be isolated from
peripheral blood of pathogen-experienced donors. The isolated CTLs will be used to investigate how HLA-F
presents peptides to CTL. Since HLA-F is predominantly expressed as open conformers, we will also
determine the effect of HLA-F open conformers on CD8+ T cell activation.
Successful completion of this proposal will reveal the antigen presentation mechanisms of HLA-F and how
HLA-F modulates CD8+ T cell responses, contributing to developing HLA-F based immunotherapies.

## Key facts

- **NIH application ID:** 10190617
- **Project number:** 1R21AI159304-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jie Geng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2021-03-09 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190617

## Citation

> US National Institutes of Health, RePORTER application 10190617, Modulation of CD8+ T Cell Responses by HLA-F (1R21AI159304-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10190617. Licensed CC0.

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