# Core Fucosylation of N-linked Glycans as a Regulator of CD8+ T cell Activation and Function

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $192,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Post-translational carbohydrate modifications are important mediators of several cellular processes including
protein turnover, cell adhesion, signal transduction, modulating receptor affinity for ligand, and apoptosis.
However, in contrast to the well-established genetic code where biological information in DNA results in the
generation of RNA which is then translated into protein, no such paradigm exists for predicting the vast array of
possible post-translational glycosylation structures that could potentially decorate a given gene product. One
such glycan modification has been defined as ‘core fucosylation’ of N-linked glycans, which occurs when L-
fucose is covalently linked via an a1,6 linkage to the initial N-acetylglucosamine that originates from the
asparagine amino acid. Although core fucosylation of N-linked glycans is necessary for normal development and
physiology, whether these N-linked glycans are critical regulators of T cell activation and/or function is largely
unknown. Here, we show that CD8+ T cells are decorated with N-linked glycans containing a core fucose and
that the abundance of this specialized glycan modification increases significantly following their activation both
in vitro and in vivo. Fucosyltransferase 8 (Fut8; a1,6-fucosyltransferase) is the only glycosyltransferase enzyme
in the mammalian genome that can facilitate core fucosylation of N-linked glycans and we have now generated
a novel Fut8 conditional knockout mouse that allows us to eliminate expression of Fut8 in a cell-specific manner.
Using a T cell-specific cre-recombinase, our preliminary data show that expression of Fut8 and the subsequent
generation of core fucosylated N-linked glycans is essential to maintain antigen-specific CD8+ T cell function
(e.g. production of cytokines) during chronic viral infection. Here, we propose to use our new reagent to 1) identify
the landscape of proteins expressed by activated CD8+ T cells that become decorated with core fucosylated N-
linked glycans using a mass spectrometry approach and 2) to subsequently determine the biological relevance
of this form of post-translational glycosylation in maintaining the function of antigen-specific CD8+ T cells during
chronic viral infection.

## Key facts

- **NIH application ID:** 10333397
- **Project number:** 5R21AI159401-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jeffrey C. Nolz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2021-01-25 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333397

## Citation

> US National Institutes of Health, RePORTER application 10333397, Core Fucosylation of N-linked Glycans as a Regulator of CD8+ T cell Activation and Function (5R21AI159401-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10333397. Licensed CC0.

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