Evidence map›Paper›PMID 38354703›Full record

ArticleImmunity2024

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.

Anna H Lippert, Christopher Paluch, Meike Gaglioni, Mai T Vuong, James McColl, Edward Jenkins, Martin Fellermeyer, Joseph Clarke, Sumana Sharma, Sara Moreira da Silva and 25 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Review
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  11. Review
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  14. Article
  15. Exploring new frontiers in LAG-3 biology and therapeutics.Trends in pharmacological sciences · 2025
    Review
  16. A Human Tumor-Immune Organoid Model of Glioblastoma.bioRxiv : the preprint server for biology · 2025
    Article
  17. Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  18. Review
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 4 institutions in 2 countries.

Anna H LippertDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Christopher PaluchMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK; MiroBio Ltd, Winchester House, Oxford Science Park, Oxford, UK.
Meike GaglioniMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Mai T VuongMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
James McCollDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Edward JenkinsMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Martin FellermeyerMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Joseph ClarkeMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Sumana SharmaMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Sara Moreira da SilvaMiroBio Ltd, Winchester House, Oxford Science Park, Oxford, UK.
Billur AkkayaMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Consuelo AnzilottiMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sara H MorganMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Claire F JessupMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Markus KörbelDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Uzi GileadiMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Judith LeitnerDivision of Immune Receptors and T cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Rachel KnoxMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Mami ChirifuMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Jiandong HuoMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Susan YuMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Nicole AshmanMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Yuan LuiMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Ian WilkinsonAbsolute Antibody Ltd, Redcar, Cleveland, UK.
Kathrine E AttfieldMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Lars FuggerMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Nathan J RobertsonMiroBio Ltd, Winchester House, Oxford Science Park, Oxford, UK.
Christopher J LynchMiroBio Ltd, Winchester House, Oxford Science Park, Oxford, UK.
Lynne MurrayMiroBio Ltd, Winchester House, Oxford Science Park, Oxford, UK.
Peter SteinbergerDivision of Immune Receptors and T cell Activation, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Ana Mafalda SantosMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Steven F LeeDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Richard J CornallMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Nuffield Department of Medicine, University of Oxford, Oxford, UK. Electronic address: richard.cornall@ndm.ox.ac.uk.
David KlenermanDepartment of Chemistry, University of Cambridge, Cambridge, UK. Electronic address: dk10012@cam.ac.uk.
Simon J DavisMRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK; Radcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. Electronic address: simon.davis@imm.ox.ac.uk.
John Radcliffe Hospital · GBUniversity of Cambridge · GBScience Oxford · GBMedical University of Vienna · AT

Funding

Deciphering the specificity and molecular mechanisms of regulatory T cells using novel approachesDP2AI154451 · NIAID · OHIO STATE UNIVERSITY · PI Billur Akkaya · 2022 to 2026
$2.3M
Medical Research Council MC_UU_12010/4NIAID NIH HHS DP2 AI154451Wellcome Trust 207547Wellcome Trust 207547/Z/17/Z
6 · The paper itself

Abstract

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.

Indexed as

Protein Tyrosine PhosphatasesSignal TransductionCD28 AntigensReceptors, ImmunologicCD28 AntigensProtein Tyrosine PhosphatasesReceptors, Immunologicantibodyautoimmunitycancerimmune checkpointimmune receptorimmunotherapykinetic-segregation modelreceptor agonism

Identifiers

PMID38354703
PMCPMC7618792
OpenAlexW4391773261

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Registered trials

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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 OpenQuestion graph.