# Molecular Mechanisms for Carbohydrate Presentation to CD4+ T cells by MHCII Pathway

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $375,000

## Abstract

Project Summary/Abstract
Most pathogenic bacteria express surface carbohydrates called capsular polysaccharides (CPSs). CPSs are
important vaccine candidates given that they are located on the outermost surface of bacteria and they have
distinct structures. These two features make them easily accessible and distinctly recognizable by immune
surveillance, therefore resulting in production of CPS specific antibodies by B cells. To induce a CPS specific
adaptive immune response (i.e., T cell-mediated B cell response), CPSs are conjugated with carrier proteins,
and the conjugation products are called glycoconjugate vaccines. Due to insufficient understanding of their
immune activation mechanisms, current glycoconjugate vaccine strategies have reached saturation and are
largely modifications of past empirical conjugation methods. The production of the current generation of
glycoconjugate vaccines is based on trial and error and does not make use of specific scientific knowledge to
maximize stimulation of critical immune cells (i.e., helper T cells) involved in producing protective IgG
antibodies. A new perspective to carbohydrate-based vaccine research is much needed. With the potential of
establishing a new paradigm, our previous discovery and preliminary data demonstrate that the mammalian
CD4+ T cell repertoire contains a population of carbohydrate-specific T cells (i.e., Tcarbs) that recognize
carbohydrate epitopes. Here, we propose to expand on our previous discovery and define the molecular
mechanisms for Tcarb activation by carbohydrate epitopes from a model glycoconjugate vaccine. In Aim 1 of
this proposal we will elucidate structural requirements for carbohydrate presentation by major histocompatibility
complex class II (MHCII) proteins on the surface of antigen presenting cells (APCs) or as purified MHCII
proteins via interaction studies. In Aim 2 we will structurally and functionally characterize T cell receptor (TCR)
recognition of glycan epitopes by Tcarbs. We believe our proposed studies will create a new platform to
develop knowledge-based glycoconjugate vaccines that are enriched for functional Tcarb epitopes. Using the
discovery of Tcarb activation mechanisms and of structures of glycan epitopes, we can design and develop
new-generation glycoconjugate vaccines that will elicit strong and long lasting immune response to protect
from bacterial infections.

## Key facts

- **NIH application ID:** 9919487
- **Project number:** 5R01AI123383-05
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Fikri Y Avci
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 2016-06-06 → 2022-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919487

## Citation

> US National Institutes of Health, RePORTER application 9919487, Molecular Mechanisms for Carbohydrate Presentation to CD4+ T cells by MHCII Pathway (5R01AI123383-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9919487. Licensed CC0.

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