Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP.
Assembly of MHC class I-beta 2 microglobulin (beta 2m) dimers in the endoplasmic reticulum involves two chaperones. Calnexin has previously been shown to interact with free class I heavy chains. Here, we show that the related chaperone, calreticulin, binds human class I-beta 2m dimers prior to peptide loading. Calreticulin remains associated with at least a subset of class I molecules when they, in turn, bind to TAP. Further evidence suggests that the interaction of class I-beta 2m dimers with TAP occurs via a novel uncharacterized 48 kDa glycoprotein, tapasin, which can bind independently to TAP and class I-beta 2m-calreticulin complexes. Tapasin is absent from the mutant cell line .220, in which class I-TAP association and peptide loading is defective.
Sadasivan
B
B
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Lehner
P J
PJ
Ortmann
B
B
Spies
T
T
Cresswell
P
P
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D037282:Calreticulin; D002460:Cell Line; D006023:Glycoproteins / Q000502:physiology*; D015234:HLA-A Antigens / Q000187:drug effects / Q000378:metabolism; D015235:HLA-B Antigens / Q000187:drug effects / Q000378:metabolism; D015236:HLA-C Antigens / Q000187:drug effects / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D018832:Molecular Chaperones / Q000502:physiology*; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D012261:Ribonucleoproteins / Q000502:physiology*; D001613:beta 2-Microglobulin / Q000378:metabolism; D054836:Indolizidines
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D006023:Glycoproteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D007212:Indolizines; D018832:Molecular Chaperones; D010455:Peptides; D012261:Ribonucleoproteins; D001613:beta 2-Microglobulin; C035524:HLA-A29 antigen; C079077:HLA-B61 antigen; C048767:HLA-C*02 antigen; C073119:TAP1 protein, human; C037806:castanospermine; D054836:Indolizidines