Mapping the immunopeptidome of seven SARS-CoV-2 antigens across common HLA haplotypes

Asolina Braun, Louise C. Rowntree, Ziyi Huang, Kirti Pandey, Nikolas Thuesen, Chen Li, Jan Petersen, Dene R. Littler, Shabana Raji, Thi H.O. Nguyen, Emma Jappe Lange, Gry Persson, Michael Schantz Klausen, Jens Kringelum, Shanzou Chung, Nathan P. Croft, Pouya Faridi, Rochelle Ayala, Jamie Rossjohn, Patricia T. IllingKatherine E. Scull, Sri Ramarathinam, Nicole A. Mifsud, Katherine Kedzierska, Anders Bundgård Sørensen, Anthony W. Purcell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Most COVID-19 vaccines elicit immunity against the SARS-CoV-2 Spike protein. However, Spike protein mutations in emerging strains and immune evasion by the SARS-CoV-2 virus demonstrates the need to develop more broadly targeting vaccines. To facilitate this, we use mass spectrometry to identify immunopeptides derived from seven relatively conserved structural and non-structural SARS-CoV-2 proteins (N, E, Nsp1/4/5/8/9). We use two different B-lymphoblastoid cell lines to map Human Leukocyte Antigen (HLA) class I and class II immunopeptidomes covering some of the prevalent HLA types across the global human population. We employ DNA plasmid transfection and direct antigen delivery approaches to sample different antigens and find 248 unique HLA class I and HLA class II bound peptides with 71 derived from N, 12 from E, 28 from Nsp1, 19 from Nsp4, 73 from Nsp8 and 45 peptides derived from Nsp9. Over half of the viral peptides are unpublished. T cell reactivity tested against 56 of the detected peptides shows CD8+ and CD4+ T cell responses against several peptides from the N, E, and Nsp9 proteins. Results from this study will aid the development of next-generation COVID vaccines targeting epitopes from across a number of SARS-CoV-2 proteins.

Original languageEnglish
Article number7547
Number of pages12
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - Dec 2024

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