PXD051190

PXD051190 is an original dataset announced via ProteomeXchange.

Title	Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
Description	HLA class I (HLA-I) molecules play a central role for both NK and T-cell responses that prevent serious human cytomegalovirus (HCMV) disease. To create opportunities for viral spread, multifaceted HCMV-encoded immunoevasins target HLA-I. Among these, the glycoprotein US10 is so far insufficiently studied. While US10 has been shown to interfere with HLA-G expression, its ability to block classical HLA-I antigen presentation remains unknown. In this study, we demonstrate that US10 recognizes and binds to all HLA-I (HLA-A,-B,-C,-E,-G) heavy chains. Additionally, impaired recruitment of HLA-I to the peptide loading complex was observed. Notably, the associated effects varied significantly dependent on HLA-I genotype and allotype: i) HLA-A molecules evaded down-regulation by US10, ii) tapasin-dependent HLA-B molecules showed impaired maturation and cell surface expression, iii) β2m-assembled HLA-C, in particular HLA-C*05:01 and -C*12:03, and HLA-G were strongly retained in complex with US10 in the endoplasmic reticulum. These genotype-specific effects on HLA-I were confirmed through unbiased HLA-I ligandome analysis. Thus, the US10-mediated impact on HLA-I results in geno- and allotypic differences in a so far unparalleled and multimodal manner.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:52:28.786.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiara Noemi-Marie Mireisz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C; 3x(2)H labeled L-leucine; 6x(13)C labeled L-leucine; (2)H deuterium labeled residue; 6x(13)C labeled L-arginine
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-04 03:04:19	ID requested
⏵ 1	2024-10-07 13:52:29	announced

Gerke C, Bauersfeld L, Schirmeister I, Mireisz CN, Oberhardt V, Mery L, Wu D, J, ü, rges CS, Spaapen RM, Mussolino C, Le-Trilling VTK, Trilling M, D, ö, lken L, Paster W, Erhard F, Hofmann M, Schlosser A, Hengel H, Momburg F, Halenius A, Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning. Elife, 13():(2024) [pubmed]

10.7554/elife.85560;

submitter keyword: Antigen presentation, Immune evasion,Human cytomegalovirus

Andreas Schlosser
contact affiliation	Rudolf Virchow Center, Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany
contact email	andreas.schlosser@uni-wuerzburg.de
lab head
Chiara Noemi-Marie Mireisz
contact affiliation	Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Germany
contact email	noemi.mireisz@uni-wuerzburg.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/2024/07/PXD051190

PRIDE project URI

• PRIDE
  1. PXD051190
     1. Label: PRIDE project
     2. Name: Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning