ArticleScientific reports2015
pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity.
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 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Generation and MHC class II loading of an endogenous influenza epitope revealed by a T cell receptor-like antibody.bioRxiv : the preprint server for biology · 2026Article
- A general system for targeting MHC class II-antigen complex via a single adaptable loop.Nature biotechnology · 2025Article
- A general platform for targeting MHC-II antigens via a single loop.bioRxiv : the preprint server for biology · 2024Article
- Tuning DO:DM Ratios Modulates MHC Class II Immunopeptidomes.Molecular & cellular proteomics : MCP · 2022Article
- Yeast display of MHC-II enables rapid identification of peptide ligands from protein antigens (RIPPA).Cellular & molecular immunology · 2021Article
- In vivo clonal expansion and phenotypes of hypocretin-specific CD4Nature communications · 2019Article
- Synergy between B cell receptor/antigen uptake and MHCII peptide editing relies on HLA-DO tuning.Scientific reports · 2019Article
- Epitope Selection for HLA-DQ2 Presentation: Implications for Celiac Disease and Viral Defense.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- HLA-DO Modulates the Diversity of the MHC-II Self-peptidome.Molecular & cellular proteomics : MCP · 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
- A Missing Switch in Peptide Exchange for MHC Class II Molecules.Frontiers in immunology · 2019Review
- Introduction: MHC/KIR and governance of specificity.Immunogenetics · 2017Review
- The Other Function: Class II-Restricted Antigen Presentation by B Cells.Frontiers in immunology · 2017Review
- Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.Open biology · 2016Review
- The melting pot of the MHC II peptidome.Current opinion in immunology · 2016Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The peptide-exchange catalyst, HLA-DM, and its inhibitor, HLA-DO control endosomal generation of peptide/class II major histocompatibility protein (MHC-II) complexes; these complexes traffic to the cell surface for inspection by CD4+ T cells. Some evidence suggests that pH influences DO regulation of DM function, but pH also affects the stability of polymorphic MHC-II proteins, spontaneous peptide loading, DM/MHC-II interactions and DM catalytic activity, imposing challenges on approaches to determine pH effects on DM-DO function and their mechanistic basis. Using optimized biochemical methods, we dissected pH-dependence of spontaneous and DM-DO-mediated class II peptide exchange and identified an MHC-II allele-independent relationship between pH, DO/DM ratio and efficient peptide exchange. We demonstrate that active, free DM is generated from DM-DO complexes at late endosomal/lysosomal pH due to irreversible, acid-promoted DO destruction rather than DO/DM molecular dissociation. Any soluble DM that remains in complex with DO stays inert. pH-exposure of DM-DO in cell lysates corroborates such a pH-regulated mechanism, suggesting acid-activated generation of functional DM in DO-expressing cells.
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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.