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

The Two-State Receptor Model01:29

The Two-State Receptor Model

2.9K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
2.9K
Antigen Processing Pathways01:31

Antigen Processing Pathways

1.8K
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...
1.8K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

5.3K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.3K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

3.8K
3.8K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.4K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
8.4K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

980
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...
980

You might also read

Related Articles

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

Sort by
Same author

Mapping the TCR landscape: computational tools empowering translational immunology and therapy design.

Journal for immunotherapy of cancer·2026
Same author

Multiple autologous tumor-infiltrating lymphocyte (LM103 infusion) therapy combined with immune checkpoint inhibitor induces repeated tumor regression in a patient with aggressive mucosal melanoma: a case report and literature review.

Frontiers in oncology·2026
Same author

Intratumoral sotigalimab with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: A phase I/II study.

Cancer discovery·2026
Same author

Introduction to Markov State Modeling of Conformational Dynamics.

Journal of chemical theory and computation·2026
Same author

FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer.

Cancer immunology research·2026
Same author

STEGG: Structural TCR-pMHC ensemble generator and gallery.

Journal of molecular biology·2026

Related Experiment Video

Updated: Nov 30, 2025

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
09:32

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

14.4K

Markov state modeling reveals alternative unbinding pathways for peptide-MHC complexes.

Jayvee R Abella1, Dinler Antunes1, Kyle Jackson2

  • 1Department of Computer Science, Rice University, Houston, TX 77005.

Proceedings of the National Academy of Sciences of the United States of America
|November 13, 2020
PubMed
Summary

Understanding peptide-major histocompatibility complex (MHC) binding is key for immunotherapies. This study reveals secondary interactions, particularly at nonanchor position 4, significantly impact peptide-MHC complex stability, refining prediction models.

Keywords:
Markov state modelingadaptive samplingcompetitive binding assaypeptide–MHC binding stability

More Related Videos

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

10.1K
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
11:17

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin

Published on: March 10, 2021

6.6K

Related Experiment Videos

Last Updated: Nov 30, 2025

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
09:32

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

14.4K
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

10.1K
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
11:17

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin

Published on: March 10, 2021

6.6K

Area of Science:

  • Immunology
  • Computational Biology
  • Structural Biology

Background:

  • Peptide binding to Major Histocompatibility Complexes (MHCs) is crucial for adaptive immunity and immunotherapy development.
  • Current MHC-binding prediction methods often overlook conformational states and underestimate secondary interactions' impact on complex stability.

Purpose of the Study:

  • To develop an atomically detailed analysis framework for peptide-MHC binding stability.
  • To investigate the contributions of both anchor and nonanchor positions to peptide-MHC complex stability.
  • To improve computational models for predicting peptide-MHC interactions.

Main Methods:

  • Utilized umbrella sampling and adaptive sampling to generate a Markov state model (MSM).
  • Analyzed a specific peptide (QFKDNVILL) bound to a human MHC receptor (HLA-A24:02).
  • Simulated peptide mutations (D4A, D4P) and validated predictions with competitive binding assays.

Main Results:

  • Reaffirmed the critical role of anchor positions in stable peptide-MHC binding.
  • Identified nonanchor position 4 (p4) as having underestimated importance for complex stability.
  • MSM analysis revealed distinct unbinding pathways for wild-type versus mutated peptides.

Conclusions:

  • The developed simulation framework provides an atomically detailed analysis of peptide-MHC binding stability.
  • Nonanchor positions, especially p4, play a significant role in peptide-MHC complex stability, necessitating their inclusion in predictive models.
  • This approach can be applied to various peptide-MHC complexes, advancing MHC class I pathway modeling for immunotherapy design.