Evidence map›Paper›PMID 36520493›Full record

ArticleThe Journal of cell biology2023

Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors.

Casey Beppler, John Eichorst, Kyle Marchuk, En Cai, Carlos A Castellanos, Venkataraman Sriram, Kole T Roybal, Matthew F Krummel

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Naive CD4iScience · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Microvilli's grip on T cell development.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Review
  9. Article
  10. Article
  11. The physical landscape of CAR-T synapse.Biophysical journal · 2024
    Review
  12. Review
  13. Pre-organized landscape of T cell surface.Frontiers in immunology · 2023
    Review
  14. Review
  15. 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

8 authors at 1 institution in 1 country.

Casey BepplerDepartment of Pathology and ImmunoX, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9241-2413
John EichorstBiological Imaging Development CoLab, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-9139-9317
Kyle MarchukBiological Imaging Development CoLab, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-0169-7439
En CaiDepartment of Pathology and ImmunoX, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-8212-8387
Carlos A CastellanosDepartment of Microbiology and Immunology, Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3615-2009
Venkataraman SriramFoundery Innovations, San Francisco, CA, USA.ORCID 0000-0003-3433-5258
Kole T Roybal *Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3030-7954
Matthew F Krummel *Department of Pathology and ImmunoX, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7915-3533
University of California, San Francisco · US

Funding

Spatiotemporal Control of T cell Synapse Stabilization and SignalingR01AI052116 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2002 to 2022
$8.3M
CONTROL OF T CELL SYNAPSE STABILIZATION AND SIGNALINGR37AI052116 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHEW F KRUMMEL · 2023 to 2026
$2.5M
NIAID NIH HHS R01 AI052116NIAID NIH HHS R37 AI052116NIH HHS R01 AI052116
6 · The paper itself

Abstract

T cells typically recognize their ligands using a defined cell biology-the scanning of their membrane microvilli (MV) to palpate their environment-while that same membrane scaffolds T cell receptors (TCRs) that can signal upon ligand binding. Chimeric antigen receptors (CARs) present both a therapeutic promise and a tractable means to study the interplay between receptor affinity, MV dynamics and T cell function. CARs are often built using single-chain variable fragments (scFvs) with far greater affinity than that of natural TCRs. We used high-resolution lattice lightsheet (LLS) and total internal reflection fluorescence (TIRF) imaging to visualize MV scanning in the context of variations in CAR design. This demonstrated that conventional CARs hyper-stabilized microvillar contacts relative to TCRs. Reducing receptor affinity, antigen density, and/or multiplicity of receptor binding sites normalized microvillar dynamics and synapse resolution, and effector functions improved with reduced affinity and/or antigen density, highlighting the importance of understanding the underlying cell biology when designing receptors for optimal antigen engagement.

Indexed as

MicrovilliReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesAntigensHumansSingle-Chain AntibodiesAntigensReceptors, Antigen, T-CellReceptors, Chimeric AntigenSingle-Chain Antibodies

Identifiers

PMID36520493
PMCPMC9757849
OpenAlexW4311741065

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.