PXD027408

PXD027408 is an original dataset announced via ProteomeXchange.

Title	Viral immune evasions differentially impact cell surface presentation of MHC I allomorphs already at the peptide-loading complex
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_05:29:53.914.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marie Barth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-19 02:37:32	ID requested
⏵ 1	2022-02-17 05:29:54	announced

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]

submitter keyword: mass spectrometry, ER quality control, MHC I biogenesis, major histocompatibility complex class I, peptide-loading complex, viral immune evasion

Carla Schmidt
contact affiliation	Interdisciplinary research center HALOmem, Institute of Biochemistry and Biotechnology, Charles Tanford Protein Center, Martin Luther University Halle-Wittenberg, Halle, Germany
contact email	carla.schmidt@biochemtech.uni-halle.de
lab head
Marie Barth
contact affiliation	HALOmem, Martin Luther University Halle-Wittenberg
contact email	marie.barth@bct.uni-halle.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD027408

PRIDE project URI

• PRIDE
  1. PXD027408
     1. Label: PRIDE project
     2. Name: Viral immune evasions differentially impact cell surface presentation of MHC I allomorphs already at the peptide-loading complex