# IMMUNOBIOLOGY OF MHC RESTRICTION OF T-CELLS

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1993 · $234,081

## Abstract

Antigen presentation is an obligatory step in the development of specific
antibody and cellular immune responses that protect individuals from
infection. Understanding this process should lead to novel approaches to
control immune responses including the development new and more effective
vaccines. The theme of this project remains the analysis of how antigens
(Ags) are processed and presented to T lymphocytes. The central hypothesis
of this project is that class I Ag processing involves the cleavage of Ags
into peptides through the action of intracellular proteanases. There are
3 specific Aims:

1. What is the role of ubiquitin and the 265 proteasome in class I Ag
presentation? The goals of this Aim are: (i) To evaluate whether and to
what extent Ub and the 26S proteasome play a role in the processing of
endogenous Ags for class I presentation; and, (ii) To test the hypothesis
that the rate of degradation of Ags in the cytosol is a critical parameter
that influences the efficiency of class I presentation. The experimental
approach is to analyze whether blocking or enhancing degradation by the
Ub-proteasome pathway of degradation affects class I-restricted Ag
presentation. These studies will define the role of a major catabolic
pathway in Ag processing. In addition, these experiments will define how
degradation may control the immunogenicity of intracellular Ags and could
provide a rationale strategy for designing more active vaccines.

2. Does a form of the proteasome generate appropriate peptides for class
I presentation? The goal of this Aim is to examine whether the proteasome
generates antigenic peptides and whether its activity/specificity is
immunologically-regulated. The experimental approach will be to analyze in
cell free systems the activity and specificity of the various forms of the
proteasome from normal, mutant or interferon-stimulated cells. These
experiments will define whether the 205 or 265 proteasome produce one or
both appropriate cleavages for immunogenic peptides and what role the MHC-
encoded subunits may play in this process.

3. How does a subset of APCs process exogenous Ags for MHC class I
presentation? The goal of this Aim is to define the apparently novel
pathway through which some APCs processes exogenous Ag. The experimental
approach will use mutant (targeted gene disruption) and cloned-lines of
these APCs in studies that will directly follow the fate of Ag and in
experiments using modified-Ags and selective inhibitors to probe the key
steps in this pathway.

## Key facts

- **NIH application ID:** 3129792
- **Project number:** 2R01AI020248-11
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** KENNETH L ROCK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $234,081
- **Award type:** 2
- **Project period:** 1983-08-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129792

## Citation

> US National Institutes of Health, RePORTER application 3129792, IMMUNOBIOLOGY OF MHC RESTRICTION OF T-CELLS (2R01AI020248-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129792. Licensed CC0.

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