# HLA class I peptidome diversities and CD8+ T cell responses to COVID-19 vaccines

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $188,280

## Abstract

CD8+ T cells recognize short peptide antigens in the context of major histocompatibility complex class I (MHC-
I) proteins. Three sets of genes, the human leukocyte antigens (HLA) HLA-A, HLA-B and HLA-C encode the
heavy chains of human MHC-I (HLA-I) proteins, which also contain a light chain (β2-microglobulin) and a
peptide. The HLA-A, HLA-B and HLA-C genes are highly polymorphic. In cells, individual HLA-I allotypes can
bind to many peptides derived from intracellular proteins. Cell infection induces the binding of specific
pathogen-derived peptides, which can trigger CD8+ T cell recognition and immunity. Recent mass
spectrometric (MS) studies have identified the sequences of thousands of peptides that bind to HLA-I
allotypes, the individual peptidomes. Inspections of these peptide sequences lead to the hypothesis of variable
peptide repertoire sizes among HLA-I allotypes and resulting variations in the breadth of CD8+ T cell responses
to SARS-Cov2 infection and COVID-19 vaccination. To address this hypothesis, in the proposed studies,
quantitative high resolution mass spectrometry (MS) will be used to measure differences in self-peptide
repertoire sizes for selected HLA-B allotypes. Factors that underlie variations in repertoire sizes will be
examined. Additionally, the breadth of SARS-CoV-2 Spike epitopes that induce CD8+ T cell activation will be
measured using blood from select HLA genotyped blood donors who have been vaccinated against COVID-19,
examining the prevalence of epitope breadth variations among HLA-I allotypes. Taken together, these studies
address the prevalence and consequences of variable HLA-I peptidome diversities, with a focus on immunity
induced by COVID-19 vaccines. The knowledge resulting from these studies will inform on key aspects of HLA-
I biology and vaccine-indued immunity.

## Key facts

- **NIH application ID:** 10523733
- **Project number:** 1R21AI164025-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MALINI RAGHAVAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $188,280
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523733

## Citation

> US National Institutes of Health, RePORTER application 10523733, HLA class I peptidome diversities and CD8+ T cell responses to COVID-19 vaccines (1R21AI164025-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10523733. Licensed CC0.

---

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