Open AccessT cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E derived from infected human cells
Author(s) -
Curtis P. McMurtrey,
Melanie J. Harriff,
Gwendolyn Swarbrick,
Amanda Duncan,
Meghan Cansler,
Megan,
Wilfried Bardet,
Kenneth W. Jackson,
Deborah A. Lewinsohn,
William H. Hildebrand,
David Lewinsohn
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0188288
Subject(s) - human leukocyte antigen , mycobacterium tuberculosis , cd8 , tuberculosis , major histocompatibility complex , biology , t cell , antigen , peptide , t cell receptor , immunology , cytotoxic t cell , epitope , immune system , virology , medicine , biochemistry , in vitro , pathology
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 Rv0634A 19-29 peptide. Further evaluation of this immunodominant peptide response confirmed HLA-E restriction and the presence of Rv0634A 19-29 -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.