Evidence map›Paper›PMID 35320345›Full record

ArticleThe Journal of experimental medicine2022

The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling.

Oscar A Aguilar, Lam-Kiu Fong, Kenichi Ishiyama, William F DeGrado, Lewis L Lanier

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

20 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. FcγRIIIa is a noncanonical costimulatory molecule for CD8 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. American journal of respiratory and critical care medicine · 2024
    Observational
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

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

5 authors at 1 institution in 1 country.

Oscar A AguilarDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-7990-8745
Lam-Kiu FongDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-8586-7548
Kenichi IshiyamaDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-9377-2098
William F DeGradoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-4745-263X
Lewis L LanierDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-1308-3952
University of California, San Francisco · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
NK MemoryR01AI068129 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANIER, LEWIS LEE · 2006 to 2020
$6.0M
Modeling Antibody-induced Immune Responses by NK cells in Mice and Humans (Resubmission 1)R01AI146581 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI DAS, JAYAJIT · 2020 to 2025
$2.3M
BD FACSAria Fusion Cell SorterS10OD021822 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, MICHAEL R. · 2016 to 2016
$573k
Modeling Antibody-induced Immune Responses by NK cells in Mice and HumansR56AI146581 · NIAID · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI DAS, JAYAJIT · 2019 to 2019
$512k
Cancer Research InstituteNIAID NIH HHS R01 AI068129NIAID NIH HHS R01 AI146581NIAID NIH HHS R56 AI146581NIDDK NIH HHS P30 DK063720NIGMS NIH HHS K12 GM081266NIH HHS P30 DK063720NIH HHS S10 OD021822
6 · The paper itself

Abstract

Natural killer (NK) cells can detect antibody-coated cells through recognition by the CD16 Fc receptor. The importance of CD16 in human NK cell biology has long been appreciated, but how CD16 functions in mouse NK cells remains poorly understood. Here, we report drastic differences between human and mouse CD16 functions in NK cells. We demonstrate that one of the adaptor molecules that CD16 associates with and signals through, CD3ζ, plays a critical role in these functional differences. Using a systematic approach, we demonstrate that residues in the transmembrane domain of the mouse CD3ζ molecule prevent efficient complex formation with mouse CD16, thereby dampening receptor function. Mutating these residues in mouse CD3ζ to those encoded by human CD3ζ resulted in rescue of CD16 receptor function. We reveal that the mouse CD3ζ transmembrane domain adopts a tightly packed confirmation, preventing association with CD16, whereas human CD3ζ adopts a versatile configuration that accommodates receptor assembly.

Indexed as

CD3 ComplexKiller Cells, NaturalReceptors, IgGAnimalsGPI-Linked ProteinsHumansMiceReceptors, FcSignal TransductionCD3 antigen, zeta chainCD3 ComplexFCGR3B protein, humanFcgr3 protein, mouseGPI-Linked ProteinsReceptors, FcReceptors, IgG

Identifiers

PMID35320345
PMCPMC8953085
OpenAlexW4221027310

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.