title: Assembly and antigen-presenting function of MHC class I molecules in cells lacking the ER chaperone calreticulin.
abstract: MHC class I molecules expressed in a calreticulin-deficient cell line (K42) assembled with beta 2-microglobulin (beta2-m) normally, but their subsequent loading with optimal peptides was defective. Suboptimally loaded class I molecules were released into the secretory pathway. This occurred despite the ability of newly synthesized class I to interact with the transporter associated with antigen processing (TAP) loading complex. The efficiency of peptide loading was reduced by 50%-80%, and impaired T cell recognition was observed for three out of four antigens tested. The peptide-loading function was specific to calreticulin, since the defect in K42 could be rectified by transfection with calreticulin but not a soluble form of calnexin, which shares its lectin-like activity.
authors.affiliation: University of Oxford, Nuffield Department of Clinical Medicine, Institute for Molecular Medicine, John Radcliffe Hospital, OX3 9DS, Oxford, United Kingdom.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Raju
authors.initials: R
authors.lastname: Adhikari
authors.forename: Mark
authors.initials: M
authors.lastname: Howarth
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Marielle C
authors.initials: MC
authors.lastname: Gold
authors.forename: Ann B
authors.initials: AB
authors.lastname: Hill
authors.forename: Rai
authors.initials: R
authors.lastname: Knee
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
authors.forename: Tim
authors.initials: T
authors.lastname: Elliott
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017920:Antiporters / Q000737:chemistry; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000502:physiology*; D037282:Calreticulin; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000737:chemistry* / Q000502:physiology; D007136:Immunoglobulins / Q000737:chemistry; D007535:Isomerases / Q000737:chemistry; D026901:Membrane Transport Proteins; D051379:Mice; D019704:Protein Disulfide-Isomerases; D012261:Ribonucleoproteins / Q000502:physiology*
chemical_list: D017920:Antiporters; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D012261:Ribonucleoproteins; C107762:tapasin; D007535:Isomerases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases