HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells

Melanie J. Harriff, Lisa M. Wolfe, Gwendolyn Swarbrick, Megan Null, Meghan E. Cansler, Elizabeth T. Canfield, Todd Vogt, Katelynne Gardner Toren, Wei Li, Mary Jackson, Deborah A. Lewinsohn, Karen M. Dobos, David M. Lewinsohn

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8+ T cells are important to the control of Mtb infection. We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8+ T cells. In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8+ T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32. Recognition by the CD8+ T cell clone required N-Terminal O-linked mannosylation of MPT32 by a mannosyltransferase encoded by the Rv1002c gene. This is the first description of a post-Translationally modified Mtb-derived protein antigen presented in the context of an HLA-E specific CD8+ T cell immune response. The identification of an immune response that targets a unique mycobacterial modification is novel and may have practical impact in the development of vaccines and diagnostics.

Original languageEnglish (US)
Article number4622
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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    Harriff, M. J., Wolfe, L. M., Swarbrick, G., Null, M., Cansler, M. E., Canfield, E. T., Vogt, T., Toren, K. G., Li, W., Jackson, M., Lewinsohn, D. A., Dobos, K. M., & Lewinsohn, D. M. (2017). HLA-E Presents Glycopeptides from the Mycobacterium tuberculosis Protein MPT32 to Human CD8+ T cells. Scientific Reports, 7(1), [4622]. https://doi.org/10.1038/s41598-017-04894-0