# A role for glycolipids and unconventional T cell subsets in alpha-gal allergy

> **NIH NIH K08** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $200,044

## Abstract

Project Summary/Abstract
 This proposal seeks to expand our understanding of the mechanisms driving alpha-gal syndrome (AGS)
and to provide a strong foundation for the applicant, Dr. Onyinye Iweala, to build an independent basic and
translational research career. The candidate is an Assistant Professor of Medicine, tenure track, at the University
of North Carolina-Chapel Hill (UNC) School of Medicine and a member of the Thurston Arthritis Research Center
and the UNC Food Allergy Initiative. The proposed project expands on her previous training in mucosal
immunology, weaving together the fields of mucosal immunity with glycolipid biology and allergic effector cell
biology in the context of a paradigm-shifting food allergy. Through formal coursework outlined in the proposal
and with help from her mentorship team, led by primary mentors Scott Commins and Wesley Burks, the
candidate will develop the technical and administrative skills needed to run a successful basic and translational
research enterprise. In the process, she will develop a unique skillset that will enhance her ability to compete
successfully for R01 grants and comparable funding mechanisms available through government agencies and
private foundations. AGS is an exciting area of food allergy ripe for discovery. By studying this condition, the
candidate will cultivate her interest in mucosal immunity and develop new expertise in glycolipid biology during
her transition from a mentored to an independent investigator.
 Alpha-gal syndrome, characterized by delayed allergic responses to red meat (mammalian meat), is a novel
allergic condition associated with tick bites and specific IgE antibody to the oligosaccharide galactose-α-1,3-
galactose (alpha-gal). Alpha-gal food allergy challenges the current paradigm for food allergy because reactions
are usually delayed, appearing >2 hours following meat ingestion; IgE antibodies are against a carbohydrate
rather than a protein; and the allergy can develop in adulthood after many years of safely tolerating red meat.
The lipid content of ingested meat appears to impact reaction consistency and severity, leading many to theorize
that alpha-gal in glycolipid form is a critical driver of symptoms in this allergy. However, no one has shown that
alpha-gal-specific (s)IgE can bind alpha-gal glycolipids or that alpha-gal glycolipids can activate allergic effector
cells. Innate or unconventional T lymphocyte populations, specifically CD1d-restricted invariant natural killer T
(iNKT) cells, bind glycolipid antigens complexed with CD1d and direct immune responses to lipid. Yet, the extent
to which this T cell population drives alpha-gal allergy remains unexplored. Our preliminary results suggest that
alpha-gal-sIgE binds mammalian glycolipids and that alpha-gal glycolipids can activate basophils sensitized with
plasma containing alpha-gal-sIgE. Moreover, activated circulating CD1d-restricted NKT cells are detectable in
alpha-gal allergic subjects. Thus, we...

## Key facts

- **NIH application ID:** 10197025
- **Project number:** 5K08AI141691-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Onyinye I Iweala
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $200,044
- **Award type:** 5
- **Project period:** 2020-06-17 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197025

## Citation

> US National Institutes of Health, RePORTER application 10197025, A role for glycolipids and unconventional T cell subsets in alpha-gal allergy (5K08AI141691-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197025. Licensed CC0.

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