Impact of peptide:HLA complex stability for the identification of SARS-CoV-2-specific CD8+T cells

Olivia Lie-Andersen, Mie Linder Hübbe, Krishanthi Subramaniam, Daniel Steen-Jensen, Ann Christina Bergmann, Daniel Justesen, Morten Orebo Holmström, Lance Turtle, Sune Justesen, Telma Lança, Morten Hansen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Induction of a lasting protective immune response is dependent on presentation of epitopes to patrolling T cells through the HLA complex. While peptide:HLA (pHLA) complex affinity alone is widely exploited for epitope selection, we demonstrate that including the pHLA complex stability as a selection parameter can significantly reduce the high false discovery rate observed with predicted affinity. In this study, pHLA complex stability was measured on three common class I alleles and 1286 overlapping 9-mer peptides derived from the SARS-CoV-2 Spike protein. Peptides were pooled based on measured stability and predicted affinity. Strikingly, stability of the pHLA complex was shown to strongly select for immunogenic epitopes able to activate functional CD8+T cells. This result was observed across the three studied alleles and in both vaccinated and convalescent COVID-19 donors. Deconvolution of peptide pools showed that specific CD8+T cells recognized one or two dominant epitopes. Moreover, SARS-CoV-2 specific CD8+T cells were detected by tetramer-staining across multiple donors. In conclusion, we show that stability analysis of pHLA is a key factor for identifying immunogenic epitopes.
Original languageEnglish
Article number1151659
JournalFrontiers in Immunology
Volume14
Number of pages10
ISSN1664-3224
DOIs
Publication statusPublished - 2023

Keywords

  • NeoScreen stability assay
  • Affinity
  • Epitope
  • COVID-19
  • Tetramer
  • pHLA
  • PBMC
  • Flow cytometry

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