title: Dipeptides catalyze rapid peptide exchange on MHC class I molecules.
abstract: Peptide ligand selection by MHC class I molecules, which occurs by iterative optimization, is the centerpiece of immunodominance in antiviral and antitumor immune responses. For its understanding, the molecular mechanisms of peptide binding and dissociation by class I molecules must be elucidated. To this end, we have investigated dipeptides that bind to the F pocket of class I molecules. We find that they accelerate the dissociation of prebound peptides of both low and high affinity, suggesting a mechanism of action for the peptide-exchange chaperone tapasin. Peptide exchange on class I molecules also has practical uses in epitope discovery and T-cell monitoring.
authors.affiliation: Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Saini
authors.affiliation: Department of Immunology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schuster
authors.affiliation: Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and.
authors.forename: Venkat Raman
authors.initials: VR
authors.lastname: Ramnarayan
authors.affiliation: Department of Immunology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Department of Immunology, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.affiliation: Molecular Life Science, Jacobs University Bremen, 28759 Bremen, Germany; and sebastian.springer@queens.oxon.org.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Springer
mesh_terms: D000595:Amino Acid Sequence; D055162:Biocatalysis; D004151:Dipeptides / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization
chemical_list: D004151:Dipeptides; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; C028544:cyclohexylalanine; D010649:Phenylalanine
keywords: MHC tetramers; dipeptides; immunotherapy; peptide exchange; tapasin