T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles

Luca Hensen, Patricia T. Illing, Louise C. Rowntree, Jane Davies, Adrian Miller, Steven Y.C. Tong, Jennifer R. Habel, Carolien E. van de Sandt, Katie L Flanagan, Anthony W. Purcell, Katherine Kedzierska, E. Bridie Clemens

Research output: Contribution to journalReview articlepeer-review

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Abstract

CD8+ T cells are a pivotal part of the immune response to viruses, playing a key role in disease outcome and providing long-lasting immunity to conserved pathogen epitopes. Understanding CD8+ T cell immunity in humans is complex due to CD8+ T cell restriction by highly polymorphic Human Leukocyte Antigen (HLA) proteins, requiring T cell epitopes to be defined for different HLA allotypes across different ethnicities. Here we evaluate strategies that have been developed to facilitate epitope identification and study immunogenic T cell responses. We describe an immunopeptidomics approach to sequence HLA-bound peptides presented on virus-infected cells by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using antigen presenting cell lines that stably express the HLA alleles characteristic of Indigenous Australians, this approach has been successfully used to comprehensively identify influenza-specific CD8+ T cell epitopes restricted by HLA allotypes predominant in Indigenous Australians, including HLA-A*24:02 and HLA-A*11:01. This is an essential step in ensuring high vaccine coverage and efficacy in Indigenous populations globally, known to be at high risk from influenza disease and other respiratory infections.

Original languageEnglish
Article number812393
Pages (from-to)1-23
Number of pages23
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 6 May 2022

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