ArticleScientific reports2015
Selector function of MHC I molecules is determined by protein plasticity.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- A specific amino acid motif ofProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Review
- HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dynamic Allostery in T Cell Receptor Specificity: A Role for Peptides and MHC Polymorphisms in Allosterically Tuning Immune Recognition.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Structural evolution of polymorphic class I HLA alleles, designating HLA-C with uncertain assemblies.Computational and structural biotechnology journal · 2026Article
- How conformational changes near the F pocket of MHC class I proteins mediate chaperone assisted peptide loading.Frontiers in immunology · 2025Article
- Evidence of focusing the MHC class I immunopeptidome by tapasin.Frontiers in immunology · 2025Article
- Structure, function, and immunomodulation of the CD8 co-receptor.Frontiers in immunology · 2024Review
- Visualising tapasin- and TAPBPR-assisted editing of major histocompatibility complex class-I immunopeptidomes.Current opinion in immunology · 2023Review
- Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.Science advances · 2023Article
- Partial peptide dissociation and binding groove plasticity in two major histocompatibility complex class I alleles - differences between allelesRSC advances · 2022Article
- Structure of an MHC I-tapasin-ERp57 editing complex defines chaperone promiscuity.Nature communications · 2022Article
- Genetic variation that determinesProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes.Cell reports · 2022Article
- Tapasin-mediated editing of the MHC I immunopeptidome is epitope specific and dependent on peptide off-rate, abundance, and level of tapasin expression.Frontiers in immunology · 2022Article
- Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins.Journal of proteome research · 2021Article
- Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules.Nature communications · 2021Article
- Dynamics of MHC-I molecules in the antigen processing and presentation pathway.Current opinion in immunology · 2021Review
- Characterization of the Class I MHC Peptidome Resulting From DNCB Exposure of HaCaT Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The selection of peptides for presentation at the surface of most nucleated cells by major histocompatibility complex class I molecules (MHC I) is crucial to the immune response in vertebrates. However, the mechanisms of the rapid selection of high affinity peptides by MHC I from amongst thousands of mostly low affinity peptides are not well understood. We developed computational systems models encoding distinct mechanistic hypotheses for two molecules, HLA-B*44:02 (B*4402) and HLA-B*44:05 (B*4405), which differ by a single residue yet lie at opposite ends of the spectrum in their intrinsic ability to select high affinity peptides. We used in vivo biochemical data to infer that a conformational intermediate of MHC I is significant for peptide selection. We used molecular dynamics simulations to show that peptide selector function correlates with protein plasticity, and confirmed this experimentally by altering the plasticity of MHC I with a single point mutation, which altered in vivo selector function in a predictable way. Finally, we investigated the mechanisms by which the co-factor tapasin influences MHC I plasticity. We propose that tapasin modulates MHC I plasticity by dynamically coupling the peptide binding region and α3 domain of MHC I allosterically, resulting in enhanced peptide selector function.
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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.