# Sialylation dependent control of CD8 T cell stemness during chronic viral infection

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $222,750

## Abstract

PROJECT SUMMARY
During chronic infections such as those caused by HIV-1, hepatitis C virus (HCV), and lymphocytic
choriomeningitis virus (LCMV), as well as during tumor outgrowth, antigen-specific CD8 T cells often
progressively lose function in a step-wise manner. Understanding the factors that impact CD8 T cell
responses during chronic viral infections is necessary for the design of effective immunotherapeutic strategies.
Recent reports demonstrate that a discrete subset of exhausted CD8 T cells exists that displays stem cell-like
properties, including the ability to self-renew and further differentiate in vivo. Importantly, this subset of cells is
exquisitely responsive to anti-PD-L1 immunotherapy during chronic LCMV clone 13 infection. Hence,
determining the mechanisms that promote the maintenance and survival of stem-like CD8 T cells during
chronic viral infection is of central importance. We present preliminary findings that show a distinct fraction of
the virus-specific stem-like CD8 T cells express cell surface N-glycans with α-2,6 linked sialic acids, a
posttranslational modification mediated by the glycosyltransferase ST6Gal-I. Importantly, published studies, as
well as our own data, establish that this enzyme is associated with pluripotency and stemness. Together,
these data lead us to hypothesize that ST6Gal-I sialylation positively regulates CD8 T cell stemness and
responsiveness to immunotherapy during chronic viral infection. Our objectives of this exploratory R21
application are to:
 Aim 1. Determine if ST6Gal-I sialylation identifies stem-like CD8 T cells during chronic viral infection.
 Aim 2: Determine how modulation of ST6Gal-I sialylation impacts CD8 T cell stemness.
Collectively, these studies are designed to provide new information regarding the impact of cell surface
sialylation of CD8 T cell responses, including CD8 T cell stemness and exhaustion.

## Key facts

- **NIH application ID:** 9820238
- **Project number:** 5R21AI142641-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Laurie Ellen Harrington
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,750
- **Award type:** 5
- **Project period:** 2018-11-07 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9820238

## Citation

> US National Institutes of Health, RePORTER application 9820238, Sialylation dependent control of CD8 T cell stemness during chronic viral infection (5R21AI142641-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9820238. Licensed CC0.

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