title: Understanding TR binding to pMHC complexes: how does a TR scan many pMHC complexes yet preferentially bind to one.
abstract: Understanding the basis of the binding of a T cell receptor (TR) to the peptide-MHC (pMHC) complex is essential due to the vital role it plays in adaptive immune response. We describe the use of computed binding (free) energy (BE), TR paratope, pMHC epitope, molecular surface electrostatic potential (MSEP) and calculated TR docking angle (θ) to analyse 61 TR/pMHC crystallographic structures to comprehend TR/pMHC interaction. In doing so, we have successfully demonstrated a novel/rational approach for θ calculation, obtained a linear correlation between BE and θ without any "codon" or amino acid preference, provided an explanation for TR ability to scan many pMHC ligands yet specifically bind one, proposed a mechanism for pMHC recognition by TR leading to T cell activation and illustrated the importance of the peptide in determining TR specificity, challenging the "germline bias" theory.
authors.affiliation: Department of Chemistry and Biomolecular Sciences and ARC Centre of Excellence in Bioinformatics, Macquarie University, Sydney, Australia.
authors.forename: Javed Mohammed
authors.initials: JM
authors.lastname: Khan
authors.forename: Shoba
authors.initials: S
authors.lastname: Ranganathan
mesh_terms: D000818:Animals; D032882:Comprehension / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013379:Substrate Specificity / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I; D046912:Multiprotein Complexes; D011948:Receptors, Antigen, T-Cell