Epitopes described in "Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers."

Reference
Article Authors:Christopher J Holland; Pierre J Rizkallah; Sabrina Vollers; J Mauricio Calvo-Calle; Florian Madura; Anna Fuller; Andrew K Sewell; Lawrence J Stern; Andrew Godkin; David K Cole
Article Title:Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers.
Reference Detail
Reference ID:1025094
Abstract:Successful immunity requires that a limited pool of T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by 'self' major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (HA(306-318)) presented by HLA-DR1 or HLA-DR4 represents an ideal system for interrogating pMHC-II antigen recognition. Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it to both complex structures. Despite a relatively rigid binding mode, HA1.7 T-cells could tolerate mutations in key contact residues within the peptide epitope. Thermodynamic analysis revealed that limited plasticity and extreme favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross-react with HA(306-318) presented by multiple MHC-II alleles.
Date:2012
Reference Type:Literature
PubMed ID:22953050
Journal:Sci Rep
Journal Volume:2
Article Pages:629
Journal ISSN:2045-2322
Article Chemical List:Epitopes;HLA-DR1 Antigen;HLA-DR4 Antigen;Receptors, Antigen, T-Cell, alpha-beta
Article MeSH List:Amino Acid Sequence; Cells, Cultured; Cross Reactions; Crystallography, X-Ray; Epitopes(chemistry; immunology); HLA-DR1 Antigen(chemistry; immunology); HLA-DR4 Antigen(chemistry; immunology); Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Lymphocyte Activation; Models, Molecular; Protein Binding; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Structure, Tertiary; Receptors, Antigen, T-Cell, alpha-beta(chemistry; immunology); T-Lymphocytes(immunology; physiology); Thermodynamics
Curation Last Updated:2014-10-03 22:47:26