# Dynamics and Tuning of the MHC II Presented Peptidome

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $448,996

## Abstract

We propose a collaborative effort to identify epitopes presented by MHC-I and MHC-II proteins in the Alzheimer’s
disease (AD) brain, and to determine whether or not these are targeted by infiltrating T cells. Comprehensive
MHC immunopeptidomes will be determined for AD brains using fresh autopsy tissue, and the resulting peptide
lists scanned for microbial antigens. Brain regions typically infiltrated by T cells in AD will be compared to
unaffected regions, to identify microbial antigens possibly driving expansion and activation of inflammatory T
cells. The overall goal of the proposed supplemental work is to characterize the MHC-presented peptidome of
the brain during Alzheimer’s disease. This work fits within the two aims of the active research project “Dynamics
and tuning of MHCII-presented peptidomes” (R01-AI137198-02). Specific Aim 1 of the active award is to
identify qualitative and quantitative differences in the MHC II self-peptidome presented by local dendritic cells in
different anatomical sites. High-density immunopeptidomes will be characterized by LC/MS/MS using methods
that currently are being optimized in work underway in the active grant. We will isolate MHC-I and MHC-II bound
peptides from diseased and healthy tissue from Alzheimer’s patients, searching for differences in antigen
presentation in regions expected to be more affected in AD as compared to another region with minimal T cell
infiltration. We will use a mouse model to test the immunogenicity of any identified antigens expressed
specifically or preferentially in brain regions relevant to AD. Specific Aim 2 of the active award is to understand
the consequences of infection and inflammation on the self and foreign MHCII peptidome. We will search for
epitopes derived from HHV-6A, HHV-7, and other microbial agents implicated in AD among the peptidomes
identified in Alzheimer’s brain tissue samples. We will focus on HHV-6A, because of its known tropism for CD4
T cells, glia, and neurons, but other viral and bacterial pathogens also will be considered. Thus the proposed
research will generate tools for a critical and rigorous look at potential linkages between AD, brain immunity, and
microbial infection, and will help to validate the linkage between AD and HHV-6/7 established by bioinformatics
approaches.

## Key facts

- **NIH application ID:** 10123821
- **Project number:** 3R01AI137198-04S1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** LAURA SANTAMBROGIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,996
- **Award type:** 3
- **Project period:** 2018-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123821

## Citation

> US National Institutes of Health, RePORTER application 10123821, Dynamics and Tuning of the MHC II Presented Peptidome (3R01AI137198-04S1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10123821. Licensed CC0.

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