Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
11 authors.
Wanlin HeCenter for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Andreas DamianouTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Iolanda VendrellTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.
Klaus FrühVaccine and Gene Therapy Institute and Division of Pathology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006.
Daowen I YinDepartment of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, United Kingdom.
Frances M BrodskyDepartment of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, United Kingdom.
Benedikt M KesslerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom.ORCID 0000-0002-8160-2446
Simon BrackenridgeCenter for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.ORCID 0000-0002-0587-7560
Persephone BorrowCenter for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.ORCID 0000-0002-3877-9780
Geraldine M GillespieCenter for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Andrew J McMichaelCenter for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.ORCID 0000-0002-9101-7478
Funding
Collaboratory of AIDS Researchers for Eradication (CARE)UM1AI164567 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAVID M. MARGOLIS · 2021 to 2026
$31.6M
Evasion of Antigen Presentation by Rhesus CytomegalovirusR01AI059457 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI FRUH, KLAUS J · 2005 to 2021
$6.2M
Non-canonical epitope presentation and antigen processing by MHC-ER01AI175459 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI Klaus J Fruh, Jonah B. Sacha · 2023 to 2026
$2.8M
CAMS | Chinese Academy of Medical Sciences Initiative for Innovative Medicine () 2018-I2M-2-002Foundation for the NIH (FNIH) AI 175459Foundation for the NIH (FNIH) UMI-A1-164567NIAID NIH HHS R01 AI059457NIAID NIH HHS R01 AI175459NIAID NIH HHS UM1 AI164567UKRI | Biotechnology and Biological Sciences Research Council (BBSRC) BB/V001221/1
6 · The paper itself
Abstract
Human Leukocyte Antigen E (HLA-E) is a nonclassical MHC class I molecule that exhibits dual immunological functions in regulating natural killer (NK) cells and T cells through unusual trafficking patterns. We previously reported that HLA-E surface expression is low and transient due to its cytoplasmic tail and dominant VL9 peptide, making it a dynamic indicator of cellular status for NK cell surveillance. Here, we identify a sequence motif in the HLA-E cytoplasmic tail that enables rapid internalization via clathrin-mediated endocytosis (CME) through interaction with the adaptor protein 2 (AP-2) complex. Following internalization, HLA-E is routed to endosomes, where the same cytoplasmic motif and peptide loading together facilitate its reappearance on the cell surface-a process influenced by valosin-containing protein (VCP). Our findings reveal previously unrecognized endosomal trafficking pathways and regulatory mechanisms that distinguish HLA-E from classical HLA class I molecules, with broad implications for understanding the immunoregulatory roles of HLA-E.
Indexed as
ClathrinEndocytosisHistocompatibility Antigens Class IValosin Containing ProteinAdaptor Protein Complex 2Amino Acid MotifsCytoplasmEndosomesHEK293 CellsHLA-E AntigensHumansKiller Cells, NaturalProtein TransportAdaptor Protein Complex 2ClathrinHistocompatibility Antigens Class IHLA-E AntigensValosin Containing ProteinVCP protein, humanclathrin-mediated endocytosiscytoplasmic tailHLA-Enonclassical MHC class Ivalosin-containing protein (VCP)
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking. · full record | Socratic