ArticleNature communications2016
MHC class II complexes sample intermediate states along the peptide exchange pathway.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Dynamic states of an MHC class I molecule during peptide exchange.Nature communications · 2026Article
- Expression and Functional Characterization of Recombinant HLA-DM.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Evidence of focusing the MHC class I immunopeptidome by tapasin.Frontiers in immunology · 2025Article
- Structural insights into human MHC-II association with invariant chain.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange.Nature chemical biology · 2023Article
- Loading dynamics of one SARS-CoV-2-derived peptide into MHC-II revealed by kinetic models.Biophysical journal · 2023Article
- HIV-1-Infected CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Sortase-Mediated Multi-Fragment Assemblies by Ligation Site Switching.Angewandte Chemie (International ed. in English) · 2022Article
- Partnering for the major histocompatibility complex class II and antigenic determinant requires flexibility and chaperons.Current opinion in immunology · 2021Review
- The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek's disease virus peptides by using an unprecedented binding motif.PLoS biology · 2021Article
- Impact of Structural Observables From Simulations to Predict the Effect of Single-Point Mutations in MHC Class II Peptide Binders.Frontiers in molecular biosciences · 2021Article
- Markov state modeling reveals alternative unbinding pathways for peptide-MHC complexes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Impact of HLA-DR Antigen Binding Cleft Rigidity on T Cell Recognition.International journal of molecular sciences · 2020Article
- HLA-Arena: A Customizable Environment for the Structural Modeling and Analysis of Peptide-HLA Complexes for Cancer Immunotherapy.JCO clinical cancer informatics · 2020Article
- HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide-binding cleft.The Journal of biological chemistry · 2020Article
- Distinct editing functions of natural HLA-DM allotypes impact antigen presentation and CD4Cellular & molecular immunology · 2020Article
- CD4NPJ vaccines · 2020Article
- PySFD: comprehensive molecular insights from significant feature differences detected among many simulated ensembles.Bioinformatics (Oxford, England) · 2019Article
- Dynamically Driven Allostery in MHC Proteins: Peptide-Dependent Tuning of Class I MHC Global Flexibility.Frontiers in immunology · 2019Article
- A Missing Switch in Peptide Exchange for MHC Class II Molecules.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR-detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII's ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual's MHC restricted immune response.
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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.