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 Concept Videos

Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

82.8K
Overview
82.8K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

14.3K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
14.3K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

1.2K
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
1.2K
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

15.6K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.6K
Antigen Processing Pathways01:31

Antigen Processing Pathways

1.9K
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
1.9K
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

2.8K
Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
2.8K

You might also read

Related Articles

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

Sort by
Same author

Balancing the efficacy and safety of chimeric antigen receptor T-cell therapy by affinity combination.

Nature communications·2026
Same author

Nasal CD4+ tissue-resident memory T cells provide cross-protective immunity to influenza.

The Journal of experimental medicine·2026
Same author

Loss of GPRC5D enhances the proliferative capacity and competitive fitness of myeloma upon anti-GPRC5D immunotherapy.

Leukemia·2026
Same author

Multiomic and Longitudinal Dissection of Immune Dynamics Associated with Parkinsonism after Ciltacabtagene Autoleucel Therapy.

Blood cancer discovery·2026
Same author

Vitamin C Conditioning Generates Tumor-Targeting CAR T Cells with Superior Cytotoxicity and Fitness in a Posttransplant Lymphoproliferative Disorder Tumor Model.

Molecular cancer therapeutics·2025
Same author

Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission.

Nature communications·2025

Related Experiment Video

Updated: Dec 15, 2025

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model
11:31

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model

Published on: August 16, 2019

8.3K

Inefficient CAR-proximal signaling blunts antigen sensitivity.

Venugopal Gudipati1, Julian Rydzek2, Iago Doel-Perez1

  • 1Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, Austria.

Nature Immunology
|July 8, 2020
PubMed
Summary

Chimeric antigen receptor (CAR) T cells show reduced sensitivity to tumor antigens compared to natural T cell receptors. Signaling deficiencies in CARs limit their effectiveness against tumors with low antigen expression.

More Related Videos

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
11:55

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Published on: March 14, 2011

14.8K
Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
12:09

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

10.2K

Related Experiment Videos

Last Updated: Dec 15, 2025

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model
11:31

High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model

Published on: August 16, 2019

8.3K
Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
11:55

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Published on: March 14, 2011

14.8K
Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
12:09

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

10.2K

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Rational design of chimeric antigen receptors (CARs) is crucial for optimizing anticancer therapies.
  • Understanding CAR engagement with tumor antigens and subsequent activation is essential for improving CAR T cell efficacy.

Purpose of the Study:

  • To analyze CAR-mediated antigen recognition and signaling at the single-molecule level.
  • To compare CAR T cell sensitivity and signaling with natural T cell receptor (TCR) recognition.
  • To identify limitations in current CAR designs that affect CAR T cell therapy outcomes.

Main Methods:

  • Quantitative, single-molecule, live-cell imaging to study CAR-antigen interactions.
  • Analysis of T cell activation and proximal signaling events upon antigen engagement.
  • Comparison of CARs and TCRs in antigen binding and ZAP-70 kinase recruitment and activation.

Main Results:

  • CAR T cell sensitivity to antigen was found to be approximately 1,000-fold lower than TCR-mediated recognition.
  • CARs demonstrated superior antigen binding within the immunological synapse compared to TCRs.
  • CARs exhibited attenuated proximal signaling due to inefficient ZAP-70 recruitment, activation, and release.

Conclusions:

  • Current CAR designs possess inherent signaling deficiencies.
  • These deficiencies limit the therapeutic efficacy of CAR T cells, particularly against tumors with low antigen expression.
  • Further optimization of CAR signaling pathways is necessary to enhance CAR T cell therapy effectiveness.