Assembly and antigen-presenting function of MHC class I molecules in cells lacking the ER chaperone calreticulin.
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.
Gao
Bin
B
University of Oxford, Nuffield Department of Clinical Medicine, Institute for Molecular Medicine, John Radcliffe Hospital, OX3 9DS, Oxford, United Kingdom.
Adhikari
Raju
R
Howarth
Mark
M
Nakamura
Kimitoshi
K
Gold
Marielle C
MC
Hill
Ann B
AB
Knee
Rai
R
Michalak
Marek
M
Elliott
Tim
T
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*
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