ArticlePLoS pathogens2010
MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 55 citations in OpenAlex.
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- Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of aJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- PANDORA: A Fast, Anchor-Restrained Modelling Protocol for Peptide: MHC Complexes.Frontiers in immunology · 2022Article
- Polymorphism analysis and supertype definition of swine leukocyte antigen class I molecules in three-way crossbred (Landrace, Duroc, and Yorkshire) pigs: implications for the vaccine development of African swine fever virus.Science China. Life sciences · 2020Article
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- An Ad/MVA vectoredNPJ vaccines · 2018Article
- The Structure of the MHC Class I Molecule of Bony Fishes Provides Insights into the Conserved Nature of the Antigen-Presenting System.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Towards the knowledge-based design of universal influenza epitope ensemble vaccines.Bioinformatics (Oxford, England) · 2016Article
- Rapid identification of bovine MHCI haplotypes in genetically divergent cattle populations using next-generation sequencing.Immunogenetics · 2016Article
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- Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains.Journal of virology · 2016Article
- The structural basis of chicken, swine and bovine CD8αα dimers provides insight into the co-evolution with MHC I in endotherm species.Scientific reports · 2016Article
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- A modern approach for epitope prediction: identification of foot-and-mouth disease virus peptides binding bovine leukocyte antigen (BoLA) class I molecules.Immunogenetics · 2015Article
- Molecular Dynamics Simulation Reveals the Selective Binding of Human Leukocyte Antigen Alleles Associated with Behçet's Disease.PloS one · 2015Article
- Characterization of binding specificities of bovine leucocyte class I molecules: impacts for rational epitope discovery.Immunogenetics · 2014Article
- Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the bovine CD8αα-BoLA-2*02201 complex.Acta crystallographica. Section F, Structural biology communications · 2014Article
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design.
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