# High-throughput identification of common CD8+ T cell responses to SIV and M. tuberculosis in rhesus macaques

> **NIH NIH R24** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $683,815

## Abstract

Project Summary/Abstract
Research towards a cure for human immunodeficiency virus (HIV) and mitigation of the impact of HIV/
tuberculosis co-infections are NIH priorities. Both research areas rely on studies of macaque monkeys
experimentally infected with simian immunodeficiency virus (SIV). Interventions to elicit effective CD8+
T cell responses to SIV and Mycobacterium tuberculosis (MTb) in macaques are under active develop-
ment. These studies are limited by the dearth of SIV- and MTb-specific CD8+ T cell responses restricted
by common macaque major histocompatibility complex (MHC) class I alleles.
We began addressing this problem in the previous grant period and identified dozens of novel CD8+
T cell responses in SIV and MTb, as well as in Zika virus, ebolavirus, and influenza. We also realized
that conventional T cell epitope discovery and characterization is unwieldy, slow, and cumbersome.
Consequently, we demonstrated that MHC class I binding to millions of peptides can be measured si-
multaneously, providing a transformative and extremely rapid way to define CD8+ T cell epitopes.
The purpose of this competitive revision is to use this new technology to define CD8+ T cell epitopes in
SIV and MTb restricted by 16 common macaque MHC class I alleles.
Specifically, we will:
 Aim 1: Identify SIV and MTb CD8+ T cell responses restricted by 16 common macaque MHC
 class I molecules. We will assess peptide binding of each 8-, 9-, 10, and 11-mer peptide in the pro-
 teomes of every SIV and SHIV genome currently in Genbank and the MTb Erdman strain using an ul-
 tradense peptide array. MHC:peptide tetramers will be produced for responses that are experimentally
validated.
 Aim 2: Define peptide binding motifs for the 16 common MHC class I molecules by determining
 the impact of every amino acid substitution at each residue in CD8+ T cell epitopes on peptide
 binding. The peptide binding motifs can be used to improve algorithms for in silico prediction of
 MHC:peptide binding.
Research resources from this study will be made available to the research community through real-time
sharing of peptide array data, deposition of experimentally validated CD8+ T cell epitopes in the Immune
Epitope Database, and distribution of MHC:peptide tetramers through the NIH Tetramer Core Facility.
Furthermore, the definition of CD8+ T cell epitopes using ultradense peptide arrays is generalizable and
could revolutionize the identification of pathogen-specific epitopes in all species, including humans.

## Key facts

- **NIH application ID:** 9851449
- **Project number:** 5R24OD017850-06
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David H. O'Connor
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $683,815
- **Award type:** 5
- **Project period:** 2014-09-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851449

## Citation

> US National Institutes of Health, RePORTER application 9851449, High-throughput identification of common CD8+ T cell responses to SIV and M. tuberculosis in rhesus macaques (5R24OD017850-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851449. Licensed CC0.

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