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

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

1.3K
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
1.3K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

14.4K
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...
14.4K
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
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

4.0K
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
4.0K
Antibody Structure01:10

Antibody Structure

65.1K
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.1K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

2.7K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.7K

You might also read

Related Articles

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

Sort by
Same author

Structural basis for conserved and distinct antigen recognition by a lineage of malaria-protective antibodies.

PLoS pathogens·2026
Same author

Mapping Allergen B- and T-Cell Epitopes: Technological Advances and Their Role in Precision Allergy Therapy.

Allergy·2026
Same author

Disulphide and sequence-encoded conformational priors guide nanobody structure prediction.

bioRxiv : the preprint server for biology·2026
Same author

Engineering of acidic pH-responsive anti-CD3 binding antibodies.

mAbs·2026
Same author

Convergent antigenic drift of the influenza hemagglutinin lateral patch across time and species.

bioRxiv : the preprint server for biology·2026
Same author

Structural and immunogenetic signatures guide CD4-mimetic HIV vaccine development.

Cell reports·2026

Related Experiment Video

Updated: Dec 26, 2025

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

11.7K

T-Cell Receptor Variable β Domains Rigidify During Affinity Maturation.

Monica L Fernández-Quintero1, Clarissa A Seidler1, Klaus R Liedl2

  • 1Institute of General, Inorganic and Theoretical Chemistry, and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, A-6020, Innsbruck, Austria.

Scientific Reports
|March 13, 2020
PubMed
Summary

Mutations enhance T-cell receptor binding to staphylococcal enterotoxin C3 (SEC3) by altering flexibility in antigen-binding sites. This study reveals how structural changes drive affinity maturation and specificity.

More Related Videos

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
16:10

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins

Published on: March 22, 2012

24.3K
Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
19:05

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay

Published on: October 30, 2015

12.7K

Related Experiment Videos

Last Updated: Dec 26, 2025

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

11.7K
A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
16:10

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins

Published on: March 22, 2012

24.3K
Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
19:05

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay

Published on: October 30, 2015

12.7K

Area of Science:

  • Immunology
  • Structural Biology
  • Computational Biophysics

Background:

  • T-cell receptors (TCRs) are crucial for adaptive immunity, recognizing antigens via their variable (V) regions.
  • Superantigens, like staphylococcal enterotoxin C3 (SEC3), can broadly activate T-cells by binding to TCRs outside the normal antigen-binding groove.
  • Understanding TCR-superantigen interactions, particularly during affinity maturation, is key to deciphering immune responses and developing therapies.

Purpose of the Study:

  • To investigate the structural and dynamic changes in T-cell receptor variable beta (TCR Vβ) chains during affinity maturation when binding to the superantigen staphylococcal enterotoxin C3 (SEC3).
  • To elucidate the role of specific mutations in modulating TCR flexibility and binding kinetics.
  • To explore the mechanism of conformational selection in TCR-superantigen interactions.

Main Methods:

  • Utilized advanced computational techniques, including metadynamics and molecular dynamics simulations, to analyze TCR-SEC3 interactions across micro- to millisecond timescales.
  • Examined structural information at different stages of affinity maturation.
  • Focused on analyzing the dynamics of complementarity determining region (CDR) loops and HV4 loops.

Main Results:

  • Energetically significant mutations were found to strongly influence the flexibility of the TCR's antigen-binding site.
  • Observed changes in the dynamics of CDR loops (especially CDR2) and the HV4 loop correlated with structural diversity, conformational thermodynamics, and kinetics of transitions.
  • Demonstrated that the affinity maturation pathway follows the principle of conformational selection, with binding-competent states existing even without antigen presence.
  • A consistent link between increased specificity and reduced flexibility was identified throughout the affinity maturation process.

Conclusions:

  • Specific mutations critically alter TCR Vβ chain dynamics, impacting antigen-binding site flexibility and driving affinity maturation towards staphylococcal enterotoxin C3 (SEC3).
  • The findings support a conformational selection mechanism, where pre-existing conformational ensembles facilitate binding.
  • Reduced flexibility is a key characteristic associated with enhanced specificity in TCR-superantigen interactions during affinity maturation.