PXD060886

PXD060886 is an original dataset announced via ProteomeXchange.

Title	A cytoplasmic tail motif directs HLA-E to clathrin-mediated endocytosis and valosin-containing-protein-mediated recycling
Description	Recent discoveries highlight the effectiveness of major histocompatibility complex (MHC)-E-restricted CD8+ T cell responses in controlling certain infections, particularly in a rhesus cytomegalovirus (RhCMV68-1)-vectored simian immunodeficiency virus (SIV) vaccine. In this context, these responses are preferentially elicited and are crucial for enabling vaccinated rhesus macaques to eradicate an SIV challenge. To harness human leukocyte antigen (HLA)-E-restricted CD8+ T cell responses for therapeutic purposes, it is essential to understand how these responses are primed, especially the mechanisms regulating MHC-E trafficking within endosomal pathways. Here, we identified a novel lysine/tryptophan-based motif in the HLA-E cytoplasmic tail that promotes rapid surface turnover via clathrin-mediated endocytosis. This motif, combined with strong binding peptides, also facilitates HLA-E recycling through a distinct valosin-containing protein-dependent pathway. Additionally, we show that this motif and its associated endosomal transport mechanisms are conserved in rhesus macaques and Mauritian-origin cynomolgus macaques. These findings advance our understanding of how MHC-E regulates immune functions through unconventional transport processes and offer insights for stimulating HLA-E-restricted CD8+ T cell responses in immunotherapy development.
HostingRepository	PRIDE
AnnounceDate	2025-11-10
AnnouncementXML	Submission_2025-11-09_16:46:18.578.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Damianou
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-17 10:05:04	ID requested
⏵ 1	2025-11-09 16:46:19	announced

10.1073/pnas.2514956122;

He W, Damianou A, Vendrell I, Fr, ü, h K, Yin DI, Brodsky FM, Kessler BM, Brackenridge S, Borrow P, Gillespie GM, McMichael AJ, A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking. Proc Natl Acad Sci U S A, 122(43):e2514956122(2025) [pubmed]

submitter keyword: Proximity Labelling,HLA-E

Prof Benedikt Kessler
contact affiliation	Professor of Biochemistry and Mass Spectrometry. University of Oxford
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Andreas Damianou
contact affiliation	University of Oxford
contact email	andreas.damianou@ndm.ox.ac.uk
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/2025/11/PXD060886

PRIDE project URI

• PRIDE
  1. PXD060886
     1. Label: PRIDE project
     2. Name: A cytoplasmic tail motif directs HLA-E to clathrin-mediated endocytosis and valosin-containing-protein-mediated recycling