# Investigating the immunomodulatory role of the Nonclassical MHC Molecule HLA-F in Human Pregnancy

> **NIH AI U01** · UNIVERSITY OF CHICAGO · 2026 · $818,457

## Abstract

Project Summary/Abstract
HLA-F is a nonclassical class I MHC (Ib) molecule that has been found expressed on a variety of cancers,
shown to play a role in HIV and adenoviral infection, the neurological autoimmune disease ALS and, relevant
to this application, is expressed throughout pregnancy. Despite the potential importance of this protein in
these conditions, little is known about this molecule in terms of its function or even in which conformational
state it is expressed. We have recently shown that, in addition to being expressed as a heavy chain only
state, or open conformer (HLA-FOC), HLA-F can also be expressed as a bon fide peptide presenting molecule,
associated with the β2m subunit (pHLA-F). Peptides are presented in an unconventional way, with the N-
terminus not anchored within the groove and the potential for post-translational modifications featuring in
peptide anchoring. Despite these advances, there remains much unknown about how these conformer states
are regulated, how it engages its various receptors in each of these conformer states, and the role of HLA-F in
reproduction. Thus, the aims of this proposal focus on addressing these questions and are: Aim 1: To identify
which cell types express HLA- F during early and late gestation in normal, healthy pregnancies,
and determine which extracellular conformer states and splice isoforms that HLA-F adopts on
these cells. Using conformer-specific antibodies, we will determine what cell types express which (or both)
forms. We will also pursue peptide elution studies from relevant cell lines to determine if the peptide differs from
non-reproductive tissue. Aim 2: To identify and analyze the factors that regulate the production or
interchange of HLA-F conformers and splice forms during gestation. We will explore the cellular
factors that may play a role in switching HLA-F between peptide-loaded and HLA-FOC as well as an intriguing
splice variant of HLA-F of unknown function. Finally, in Aim 3 we seek to esta

## Key facts

- **NIH application ID:** 11297892
- **Project number:** 1U01AI173346-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Erin June Adams
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $818,457
- **Award type:** 1
- **Project period:** 2026-04-02T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11297892

## Citation

> US National Institutes of Health, RePORTER application 11297892, Investigating the immunomodulatory role of the Nonclassical MHC Molecule HLA-F in Human Pregnancy (1U01AI173346-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/11297892. Licensed CC0.

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