# Investigating the MHC Class II-Restricted Processing Landscape of HIV-1 Antigens

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $32,737

## Abstract

Project Summary
Robust HIV-specific CD4 T cell responses are associated with decreased viral load, an increased antibody
neutralization breadth, and a slower progression to AIDS, and should therefore be considered in the
development of a protective HIV vaccine. CD4 T cells are activated by antigen-derived peptides (epitopes)
displayed in complex with MHC Class II molecules (MHCII) on the surface of an antigen presenting cell (APC).
According to the standard model, internalized antigens are catabolized (“processed”) and loaded onto MHCII in
late endosomal compartments. However, many alternative pathways have been described. These include the
recycling pathway, in which peptide is loaded onto MHCII in the early endosome, and endogenous processing,
which occurs when virally-derived antigens synthesized within infected APCs are proteolyzed and loaded onto
MHCII via a complex network of intracellular pathways. While some HIV-1 epitopes can be presented from
inactivated virus, others have been shown to be presented endogenously. However, the relative contributions
of classical and alternative pathways to the HIV-specific CD4 T cell response are not known. Additionally, our
understanding of the cell types that act as APCs during HIV-1 infection, and their relative contributions to CD4
T cell activation, is incomplete. Of note, in addition to the “professional” APCs that present peptide via MHCII,
CD4 T cells, which transiently express MHCII upon stimulation and are host cells for HIV, might act in this
capacity. Accordingly, I will investigate the abilities of human dendritic cells, macrophages, and CD4 T cells to
present HIV-1 epitopes from infectious and inactivated virus, and elucidate the cellular pathways utilized by
these APCs for peptide production and MHCII loading. In Aim 1, I will define the differential abilities of
dendritic cells, macrophages, and CD4 T cells to present epitopes from live and inactivated HIV-1 using
established in vitro antigen presentation assays. In Aim 2, I will elucidate the cellular mechanisms used by
DCs, macrophages, and CD4 T cells to present HIV antigens via MHC-II using siRNA and chemical inhibitors
targeting key aspects of the antigen processing machinery. This work will provide insights into the pathways
used by APCs to activate CD4 T cells in the context of an HIV-1 infection and has the potential to inform
rational vaccine design. This project will allow me to develop into a confident, independent researcher. This
training will expand my knowledge of cell biology and immunology and help me master valuable new technical
skills. Additionally, I will improve my communication skills, allowing me to effectively communicate the
importance of biomedical research with the public. Most importantly, this training will help me achieve my long-
term professional goal of being an independent senior scientist.

## Key facts

- **NIH application ID:** 10004493
- **Project number:** 5F31AI143387-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mary Margaret Addison
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,737
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004493

## Citation

> US National Institutes of Health, RePORTER application 10004493, Investigating the MHC Class II-Restricted Processing Landscape of HIV-1 Antigens (5F31AI143387-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004493. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*