# The Role of Ubiquitin and Ubiquitin-Like Molecules in Direct Antigen Presentation

> **NIH NIH R01** · OREGON STATE UNIVERSITY · 2020 · $352,799

## Abstract

Project Summary
DESCRIPTION. The immune system must eliminate cells of the body that have become diseased as the result
of intracellular infection or oncogenic transformation. CD8+ cytotoxic T cells are responsible for completing this
task and must be able to distinguish healthy cells from diseased ones. Major Histocompatibility Complex Class
I (MHC class I) molecules are present on most nucleated cells and are responsible for presenting antigen at
the cell surface for CD8+ T cell inspection. In order to present antigen, the MHC class I pathway relies on
binding to short peptides, created from degraded cellular proteins. When the source protein is associated with
a disease (such as a viral protein or tumor associated protein) specific CD8+ T cells will recognize the peptide-
MHC class I complex and kill the cell. Because the peptide provides the ultimate specificity in this reaction, we
are interested in understanding how these peptides are created. Our data indicates that proteins which are
rapidly degraded following their synthesis (termed Defective Ribosomal Proteins or DRiPs) are responsible for
efficiently generating a supply of peptides. This proposal seeks to determine which cellular metabolic
pathways are used to direct the rapid degradation of DRiPs and to determine if DRiPs are necessary in
physiologically relevant settings. We are focusing on the ubiquitin conjugation pathway, as ubiquitin coupling
is intimately associated with protein degradation. Ubiquitin-like proteins (UBLs) may also play a role in direct
antigen presentation. The Specific Aims of this proposal are to identify how the ubiquitin-modifying enzyme
Usp14 interacts with the antigen presentation machinery, understand why conjugation of the ubiquitin-like
molecule Nedd8 is necessary for DRiP antigen presentation, and determine which E3 ubiquitin ligases are
necessary for DRiP antigen presentation.

## Key facts

- **NIH application ID:** 9859339
- **Project number:** 5R01AI130059-04
- **Recipient organization:** OREGON STATE UNIVERSITY
- **Principal Investigator:** Brian Paul Dolan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,799
- **Award type:** 5
- **Project period:** 2017-03-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859339

## Citation

> US National Institutes of Health, RePORTER application 9859339, The Role of Ubiquitin and Ubiquitin-Like Molecules in Direct Antigen Presentation (5R01AI130059-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859339. Licensed CC0.

---

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