Data from: TAPBPR mediates peptide dissociation from MHC class I using a leucine lever
Data files
Dec 28, 2018 version files 2.87 MB
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Auxiliary file 1 - Dataset 1 HeLa_TAPBPR-WT_W632.xlsx
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Auxiliary file 10 - dataset 3 HeLa_TAPBPR-GSloop_W632.xlsx
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Auxiliary file 11 - Dataset 3 HeLa_TAPBPR-GSloopG30L_W632.xlsx
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Auxiliary file 2 - Dataset 1 HeLa_TAPBPR-GSloop _W632.xlsx
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Auxiliary file 3 - Dataset 1 HeLa_TAPBPR-GSloopG30L_W632.xlsx
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Auxiliary file 4 - dataset 2 HeLa_TAPBPR-WT_W632.xlsx
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Auxiliary file 5 - dataset 2 HeLa_TAPBPR-GSloop_W632.xlsx
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Auxiliary file 6 - dataset 2 HeLa_TAPBPR-GSloopG30L_W632.xlsx
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Auxiliary file 7a - Dataset 1 TAPBPR_Volcano_plot.xlsx
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Auxiliary file 7b - Dataset 2 TAPBPR_Volcano_plot.xlsx
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Auxiliary file 8 - dataset 2 HeLa_TAPBPR-M29_W632.xlsx
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Auxiliary file 9 - dataset 3 HeLa_TAPBPR-WT_W632.xlsx
Abstract
Tapasin and TAPBPR are known to perform peptide editing on major histocompatibility complex class I (MHC I) molecules, however, the precise molecular mechanism(s) involved in this process remain largely enigmatic. Here, using immunopeptidomics in combination with novel cell-based assays that assess TAPBPR-mediate peptide exchange, we reveal a critical role for the K22-D35 loop of TAPBPR in mediating peptide exchange on MHC I. We identify a specific leucine within this loop that enables TAPBPR to facilitate peptide dissociation from MHC I. Moreover, we delineate the molecular features of the MHC I F pocket required for TAPBPR to promote peptide dissociation in a loop-dependent manner. These data reveal that chaperone-mediated peptide editing of MHC I can occur by different mechanisms dependent on the C-terminal residue that the MHC I accommodates in its F pocket and provide novel insights that may inform the therapeutic potential of TAPBPR manipulation to increase tumour immunogenicity.