ArticleThe Journal of biological chemistry2014
Susceptibility to HLA-DM protein is determined by a dynamic conformation of major histocompatibility complex class II molecule bound with peptide.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 52 citations in OpenAlex.
- MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange.Nature chemical biology · 2023Article
- Structural Framework for Analysis of CD4+ T-Cell Epitope Dominance in Viral Fusion Proteins.Biochemistry · 2023Review
- HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.Immunity · 2023Article
- Loading dynamics of one SARS-CoV-2-derived peptide into MHC-II revealed by kinetic models.Biophysical journal · 2023Article
- An immunoinformatic approach to assessing the immunogenic capacity of alpha-neurotoxins in elapid snake venoms.Frontiers in pharmacology · 2023Article
- Peptide-dependent tuning of major histocompatibility complex motional properties and the consequences for cellular immunity.Current opinion in immunology · 2022Review
- A previously unappreciated polymorphism in the beta chain of I-AMolecular immunology · 2022Article
- Partnering for the major histocompatibility complex class II and antigenic determinant requires flexibility and chaperons.Current opinion in immunology · 2021Review
- Design of a Novel Multi-Epitope Vaccine AgainstFrontiers in immunology · 2021Article
- Article
- Impact of HLA-DR Antigen Binding Cleft Rigidity on T Cell Recognition.International journal of molecular sciences · 2020Article
- The love and hate relationship of HLA-DM/DO in the selection of immunodominant epitopes.Current opinion in immunology · 2020Review
- HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide-binding cleft.The Journal of biological chemistry · 2020Article
- Synergy between B cell receptor/antigen uptake and MHCII peptide editing relies on HLA-DO tuning.Scientific reports · 2019Article
- What to do with HLA-DO/H-2O two decades later?Immunogenetics · 2019Review
- Class II MHC antigen processing in immune tolerance and inflammation.Immunogenetics · 2019Review
- HLA-DO Modulates the Diversity of the MHC-II Self-peptidome.Molecular & cellular proteomics : MCP · 2019Article
- Dynamically Driven Allostery in MHC Proteins: Peptide-Dependent Tuning of Class I MHC Global Flexibility.Frontiers in immunology · 2019Article
- Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic Discrimination of Myelin and Exogenous Antigenic Peptides.Frontiers in immunology · 2019Article
- Integrating Experiment and Theory to Understand TCR-pMHC Dynamics.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
HLA-DM mediates the exchange of peptides loaded onto MHCII molecules during antigen presentation by a mechanism that remains unclear and controversial. Here, we investigated the sequence and structural determinants of HLA-DM interaction. Peptides interacting nonoptimally in the P1 pocket exhibited low MHCII binding affinity and kinetic instability and were highly susceptible to HLA-DM-mediated peptide exchange. These changes were accompanied by conformational alterations detected by surface plasmon resonance, SDS resistance assay, antibody binding assay, gel filtration, dynamic light scattering, small angle x-ray scattering, and NMR spectroscopy. Surprisingly, all of those changes could be reversed by substitution of the P9 pocket anchor residue. Moreover, MHCII mutations outside the P1 pocket and the HLA-DM interaction site increased HLA-DM susceptibility. These results indicate that a dynamic MHCII conformational determinant rather than P1 pocket occupancy is the key factor determining susceptibility to HLA-DM-mediated peptide exchange and provide a molecular mechanism for HLA-DM to efficiently target unstable MHCII-peptide complexes for editing and exchange those for more stable ones.
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Registered trials
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.