title: Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer.
abstract: Major histocompatibility complex (MHC) class I glycoproteins bind peptides in the endoplasmic reticulum after incorporation into the peptide-loading complex, whose core is the transporter associated with antigen processing. Other components are the chaperone calreticulin, the thiol oxidoreductase ERp57, and tapasin. Tapasin and ERp57 have been shown to exist in the peptide-loading complex as a disulfide-linked heterodimer. Here, using a cell-free system, we demonstrate that although recombinant tapasin was ineffective in recruiting MHC class I molecules and facilitating peptide binding, recombinant tapasin-ERp57 conjugates accomplished both of those functions and also 'edited' the repertoire of bound peptides to maximize their affinity. Thus, the tapasin-ERp57 conjugate is the functional unit of the peptide-loading complex that generates MHC class I molecules with stably associated peptides.
authors.affiliation: Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Wearsch
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002474:Cell-Free System; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology*; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; D011994:Recombinant Proteins; C107762:tapasin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human