T cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E derived from infected human cells

Curtis McMurtrey, Melanie J. Harriff, Gwendolyn M. Swarbrick, Amanda Duncan, Meghan Cansler, Megan Null, Wilfried Bardet, Kenneth W. Jackson, Deborah A. Lewinsohn, William Hildebrand, David M. Lewinsohn

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αβ CD8+ T cells. The goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. When tested for activity with CD8+ T cells isolated from sixteen donors, nine of the ligands elicited an IFN-γ response from at least one donor, with fourteen of 16 donors responding to the Rv0634A19-29 peptide. Further evaluation of this immunodominant peptide response confirmed HLA-E restriction and the presence of Rv0634A19-29-reactive CD8+ T cells in the peripheral blood of human donors. The identification of an Mtb HLA-E ligand that is commonly recognized may provide a target for a non-traditional vaccine strategy.

Original languageEnglish (US)
Article numbere0188288
JournalPloS one
Volume12
Issue number11
DOIs
StatePublished - Nov 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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