Immunopeptidomics reveals determinants of Mycobacterium tuberculosis antigen presentation on MHC class I (SureQuant data)
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ABSTRACT: CD8+ T cells contribute to protective immunity to Mycobacterium tuberculosis (Mtb), but the principles that govern presentation of Mtb peptides on MHC class I (MHC-I) on the surface of infected macrophages for CD8+ T cell recognition are incompletely understood. Here, we use internal standard parallel reaction monitoring (IS-PRM, also known as SureQuant) to rigorously validate identifications of Mtb-derived MHC-I peptides obtained in data-dependent MS analyses. We further use SureQuant to quantify presentation of Mtb peptides derived from the secreted effector proteins EsxA and EsxJ across multiple experimental conditions. We show that presentation of both EsxA- and EsxJ-derived peptides requires the activity of the mycobacterial ESX-1 type VII secretion system, possibly indicating that ESX-1-mediated phagosome membrane damage allows Mtb proteins to access MHC-I antigen processing pathways. We show that this requirement is independent of type I interferon signaling that occurs downstream of phagosome damage. Treatment with inhibitors of conventional proteolytic pathways involved in MHC-I antigen processing inhibits presentation of self peptides as expected, but does not inhibit presentation of Mtb peptides, implying an alternative or redundant mechanism of processing.
INSTRUMENT(S): Orbitrap Exploris 480
ORGANISM(S): Homo Sapiens (human) Mycobacterium Tuberculosis H37rv
TISSUE(S): Macrophage
DISEASE(S): Tuberculosis
SUBMITTER: Owen Leddy
LAB HEAD: Forest White
PROVIDER: PXD037843 | Pride | 2023-04-24
REPOSITORIES: Pride
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