Proteomics

Dataset Information

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Immunopeptidomics reveals determinants of Mycobacterium tuberculosis antigen presentation on MHC class I (SureQuant data)


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

Dataset's files

Source:
Action DRS
031622_donor_E_Mock_F3.raw Raw
031622_donor_E__Mtb_F3.raw Raw
031722_donor_E_Mock_F2.raw Raw
031722_donor_E_Mock_F4.raw Raw
031722_donor_E_Mock_F5.raw Raw
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Publications

Leveraging Immunopeptidomics To Study and Combat Infectious Disease.

Leddy Owen K OK   White Forest M FM   Bryson Bryan D BD  

mSystems 20210803 4


T cells must recognize pathogen-derived peptides bound to major histocompatibility complexes (MHCs) in order to initiate a cell-mediated immune response against an infection, or to support the development of high-affinity antibody responses. Identifying antigens presented on MHCs by infected cells and professional antigen-presenting cells (APCs) during infection may therefore provide a route toward developing new vaccines. Peptides bound to MHCs can be identified at whole-proteome scale using ma  ...[more]

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