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Major histocompatibility complex class I (MHC I) proteins provide protection from intracellular pathogens and cancer via each of a cell's MHC I molecules binding and presenting a peptide to cytotoxic T lymphocytes. MHC I genes are highly polymorphic and can have significant diversity, with polymorphisms predominantly localised in the peptide-binding groove where they can change peptide-binding specificity. However, polymorphic residues may also determine other functional properties, such as how dependent MHC I alleles are on the peptide-loading complex for optimal acquisition of peptide cargo. We describe how differences in the peptide-binding properties of two MHC I alleles correlates with altered conformational flexibility in the peptide-empty state. We hypothesise that plasticity is an intrinsic property encoded by the protein sequence, and that co-ordinated movements of the membrane-proximal and membrane-distal domains collectively determines how dependent MHC I are on the peptide-loading complex for efficient assembly with high affinity peptides.

Original publication




Journal article


Molecular immunology

Publication Date





98 - 101


Institute for Life Sciences, Building 85, M55, University of Southampton, SO17 1BJ, UK; Cancer Sciences Unit, Faculty of Medicine, University of Southampton, SO16 6YD, UK. Electronic address:


Antigen-Presenting Cells, T-Lymphocytes, Cytotoxic, Animals, Humans, Peptides, Membrane Transport Proteins, Histocompatibility Antigens Class I, Antigen Presentation, Protein Structure, Tertiary, Protein Binding, Protein Folding, Polymorphism, Genetic, Alleles, Molecular Dynamics Simulation