T cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E derived from infected human cells
Curtis McMurtreya, Melanie J. Harriffb c, Gwendolyn M. Swarbrickd, Amanda Duncand, Meghan E. Canslerd, Megan D. Nulld, Wilfried Bardeta, Kenneth W. Jacksona, Deborah Anne Lewinsohnb c d, Deborah Anne Lewinsohna b c d✉, William H. Hildebranda b c, David Michael Lewinsohnb c d✉, David Michael Lewinsohnb c d
- aDepartment of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK, United States of America
- bDepartment of Pulmonary and Critical Care Medicine, Oregon Health and Sciences University, Portland, OR, United States of America
- cVA Portland Health Care System, Portland, OR, United States of America
- dDepartment of Pediatric Medicine, Oregon Health and Sciences University, Portland, OR, United States of America
- ✉Corresponding author
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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.
TL;DRThe goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis using an in-depth mass spectrometry approach, and identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. (Semantic Scholar)