Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Antigen-independent, integrin-mediated T cell activation

K Sturmhöfel1, C Brando, F Martinon

  • 1Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

Journal of Immunology (Baltimore, Md. : 1950)
|March 1, 1995
PubMed
Summary

T cell activation can occur independently of antigen recognition. The vitronectin receptor (VNR) binding to extracellular matrix proteins, along with zeta-chain signaling, is sufficient to trigger cytokine secretion, suggesting a role in inflammatory responses.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

BRCA functional domains associated with high risk of multiple primary tumors and domain-related sensitivity to olaparib: the Prometheus Study.

ESMO open·2025
Same author

Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD).

ESMO open·2023
Same author

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge.

ESMO open·2021
Same author

Deep sequencing of the TCR-β repertoire of human forkhead box protein 3 (FoxP3)<sup>+</sup> and FoxP3<sup>-</sup> T cells suggests that they are completely distinct and non-overlapping.

Clinical and experimental immunology·2016
Same author

Raptor hunted by caspases.

Cell death & disease·2016
Same author

Labeling cells in microtiter plates for determination of [3H]thymidine uptake.

Current protocols in immunology·2008

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Integrin-mediated signaling, particularly via the vitronectin receptor (VNR), plays a crucial role in cellular responses to the extracellular matrix (ECM).
  • Gamma/delta T cells expressing V gamma 1.1/C gamma 4 are thought to be activated by VNR engagement with ECM proteins and potentially a self-antigen.
  • The precise signaling requirements for VNR-mediated T cell activation, especially in the absence of T cell receptor (TCR) engagement, remain incompletely understood.

Purpose of the Study:

  • To investigate whether T cell activation by the vitronectin receptor (VNR) requires both ECM engagement and T cell receptor (TCR) antigen recognition.
  • To determine if VNR engagement alone, in conjunction with TCR zeta-chain signaling, is sufficient to induce T cell activation.

Main Methods:

Related Experiment Videos

  • A TCR-negative, VNR-positive T cell hybridoma (TG40) was engineered to express chimeric molecules linking the TCR zeta-chain to CD8 or CD25.
  • Stimulation was achieved using ECM proteins from fetal calf serum (FCS) and assessed by interleukin-2 (IL-2) secretion.
  • Inhibition studies involved monoclonal antibodies (mAbs) against VNR, RGD peptide, and serum-free conditions.
  • Phosphorylation of the zeta-chain was analyzed, and truncated zeta-chain constructs were used to assess signaling requirements.

Main Results:

  • Transfectants constitutively secreted IL-2 when VNR was engaged by ECM proteins, indicating T cell activation.
  • This cytokine secretion was inhibited by anti-VNR mAbs, RGD peptide, and serum-free media, confirming VNR dependence.
  • VNR engagement induced zeta-chain phosphorylation, and signaling through the zeta-chain was essential for IL-2 secretion.
  • A truncated zeta-chain chimera failed to induce constitutive IL-2 secretion, highlighting the necessity of intact zeta-chain signaling.

Conclusions:

  • T cell activation, evidenced by IL-2 secretion, can be induced by vitronectin receptor (VNR) engagement with extracellular matrix (ECM) proteins, independent of T cell receptor (TCR) antigen recognition.
  • Integrin-mediated, antigen-independent activation via VNR and zeta-chain signaling is sufficient to trigger T cell cytokine production.
  • This pathway may significantly contribute to the potentiation of inflammatory responses.