ArticleJournal of immunology (Baltimore, Md. : 1950)2009
The binding of antigenic peptides to HLA-DR is influenced by interactions between pocket 6 and pocket 9.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- T cell and autoantibody recognition of nucleus-associated islet autoantigens in individuals with type 1 diabetes.Diabetologia · 2025Article
- Two DRB3 residues predictively associate with the progression to type 1 diabetes among DR3 carriers.JCI insight · 2025Article
- Optimisation of the cultured ELISpot/Fluorospot technique for the selective investigation of SARS-CoV-2 reactive central memory T cells.Frontiers in immunology · 2025Article
- The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.Frontiers in immunology · 2025Review
- Article
- High resolution HLA-DRB1 analysis and shared molecular amino acid signature of DRβ1 molecules in Occult hepatitis B infection.BMC immunology · 2022Article
- Epitope Mapping of Pathogenic Autoantigens on Sjögren's Syndrome-Susceptible Human Leukocyte Antigens Using In Silico Techniques.Journal of clinical medicine · 2022Article
- Article
- Dynamically Driven Allostery in MHC Proteins: Peptide-Dependent Tuning of Class I MHC Global Flexibility.Frontiers in immunology · 2019Article
- FVIII proteins with a modified immunodominant T-cell epitope exhibit reduced immunogenicity and normal FVIII activity.Blood advances · 2018Article
- Molecular basis for increased susceptibility of Indigenous North Americans to seropositive rheumatoid arthritis.Annals of the rheumatic diseases · 2017Article
- Current tools for predicting cancer-specific T cell immunity.Oncoimmunology · 2016Review
- Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts.Immunologic research · 2013Article
- Differential binding of pyruvate dehydrogenase complex-E2 epitopes by DRB1*08:01 and DRB1*11:01 Is predicted by their structural motifs and correlates with disease risk.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Article
- DRB1*12:01 presents a unique subset of epitopes by preferring aromatics in pocket 9.Molecular immunology · 2012Article
- HLA-DR-presented peptide repertoires derived from human monocyte-derived dendritic cells pulsed with blood coagulation factor VIII.Molecular & cellular proteomics : MCP · 2011Article
- HLA-DR1001 presents "altered-self" peptides derived from joint-associated proteins by accepting citrulline in three of its binding pockets.Arthritis and rheumatism · 2010Article
- Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model.BMC bioinformatics · 2010Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Peptide binding to class II MHC protein is commonly viewed as a combination of discrete anchor residue preferences for pockets 1, 4, 6/7, and 9. However, previous studies have suggested cooperative effects during the peptide binding process. Investigation of the DRB1*0901 binding motif demonstrated a clear interaction between peptide binding pockets 6 and 9. In agreement with prior studies, pockets 1 and 4 exhibited clear binding preferences. Previously uncharacterized pockets 6 and 7 accommodated a wide variety of residues. However, although it was previously reported that pocket 9 is completely permissive, several substitutions at this position were unable to bind. Structural modeling revealed a probable interaction between pockets 6 and 9 through beta9Lys. Additional binding studies with doubly substituted peptides confirmed that the amino acid bound within pocket 6 profoundly influences the binding preferences for pocket 9 of DRB1*0901, causing complete permissiveness of pocket 9 when a small polar residue is anchored in pocket 6 but accepting relatively few residues when a basic residue is anchored in pocket 6. The beta9Lys residue is unique to DR9 alleles. However, similar studies with doubly substituted peptides confirmed an analogous interaction effect for DRA1/B1*0301, a beta9Glu allele. Accounting for this interaction resulted in improved epitope prediction. These findings provide a structural explanation for observations that an amino acid in one pocket can influence binding elsewhere in the MHC class II peptide binding groove.
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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.