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PXD027408

PXD027408 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleViral immune evasions differentially impact cell surface presentation of MHC I allomorphs already at the peptide-loading complex
DescriptionThe transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the endoplasmic reticulum (ER) where they are loaded onto major histocompatibility class I (MHC I) molecules. Stable peptide-MHC I complexes travel to the cell surface and present their antigenic cargo to cytotoxic T lymphocytes. As central part of the peptide-loading complex (PLC), TAP is targeted by several viral proteins, which inhibit peptide translocation and thereby impact MHC I-mediated immune responses. However, it is still poorly understood whether the MHC I allotypes are differently affected by TAP inhibition. Here, we show that conditional expression of herpes simplex virus (HSV) ICP47 suppresses surface presentation of the MHC I allotypes HLA-A and HLA-C, but not of HLA-B, while expression of cytomegalovirus (CMV) US6 reduces surface levels of all allotypes. This difference is directly reflected in a specific enrichment of HLA-B molecules at US6 arrested PLC. Since ICP47 and US6 inhibit TAP in different transport-incompetent conformations, our data imply that MHC I allomorphs are preferentially recruited or trapped at the PLC leading to selective downregulation of MHC I surface presentation. Our findings suggest that viral immune evasions not only inhibit peptide supply to the ER by TAP, but also modulate the assembly and chaperone activity of the PLC.
HostingRepositoryPRIDE
AnnounceDate2022-02-17
AnnouncementXMLSubmission_2022-02-17_05:29:53.914.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMarie Barth
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-07-19 02:37:32ID requested
12022-02-17 05:29:54announced
Publication List
Sethumadhavan S, Barth M, Spaapen RM, Schmidt C, Trowitzsch S, Tamp, é R, I at the peptide-loading complex. Sci Rep, 12(1):1516(2022) [pubmed]
Keyword List
submitter keyword: mass spectrometry, ER quality control, MHC I biogenesis, major histocompatibility complex class I, peptide-loading complex, viral immune evasion
Contact List
Carla Schmidt
contact affiliationInterdisciplinary research center HALOmem, Institute of Biochemistry and Biotechnology, Charles Tanford Protein Center, Martin Luther University Halle-Wittenberg, Halle, Germany
contact emailcarla.schmidt@biochemtech.uni-halle.de
lab head
Marie Barth
contact affiliationHALOmem, Martin Luther University Halle-Wittenberg
contact emailmarie.barth@bct.uni-halle.de
dataset submitter
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