Optimization of the MHC class I peptide cargo is dependent on tapasin.
The loading of MHC class I molecules with their peptide cargo is undertaken by a multimolecular peptide loading complex within the endoplasmic reticulum. We show that MHC class I molecules can optimize their peptide repertoire over time and that this process is dependent on tapasin. Optimization of the peptide repertoire is both quantitatively and qualitatively improved by tapasin. The extent of optimization is maximal when MHC class I molecules are allowed to load within the fully assembled peptide loading complex. Finally, we identify a single natural polymorphism (116D>Y) in HLA-B*4402 that permits tapasin-independent loading of HLA-B*4405 (116Y). In the presence of tapasin, the tapasin-independent allele B*4405 (116Y) acquires a repertoire of peptides that is less optimal than the tapasin-dependent allele B*4402 (116D).
Williams
Anthony P
AP
MRC Human Immunology Unit, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Peh
Chen Au
CA
Purcell
Anthony W
AW
McCluskey
James
J
Elliott
Tim
T
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology*; D017920:Antiporters / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015796:HLA-B27 Antigen / Q000276:immunology; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology*; D007424:Intracellular Fluid; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D013997:Time Factors
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D059948:HLA-B44 Antigen; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; D010455:Peptides; C073119:TAP1 protein, human; C107762:tapasin