Unusually long major histocompatibility complex (MHC) class I–restricted epitopes are important in immunity, but their 'bulged' conformation represents a potential obstacle to αβ T cell receptor (TCR)–MHC class I docking. To elucidate how such recognition is achieved while still preserving MHC restriction, we have determined here the structure of a TCR in complex with HLA-B*3508 presenting a peptide 13 amino acids in length. This complex was atypical of TCR–peptide–MHC class I interactions, being dominated at the interface by peptide-mediated interactions. The TCR assumed two distinct orientations, swiveling on top of the centrally bulged, rigid peptide such that only limited contacts were made with MHC class I. Although the TCR-peptide recognition resembled an antibody-antigen interaction, the TCR–MHC class I contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our findings simultaneously demonstrate the considerable adaptability of the TCR and the 'shape' of MHC restriction.
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We thank A. Brooks and D. El-hassen for discussions and reagents; P. Doherty, F. Carbone and S. Turner for critical reading of the manuscript; and the BioCars staff for assistance in data collection at Advanced Photon Source (Chicago, Illinois). J.R. and J.M. are joint senior authors. Supported by the National Health and Medical Research Council Australia, Roche Organ Transplantation Research Fund, Australian Research Council, National Health and Medical Research Council Career Development Award (S.B.), National Health and Medical Research Council Peter Doherty Training Fellowship (T.B.) and Wellcome Trust (J.R.).
The authors declare no competing financial interests.
About this article
Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study
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