TY - JOUR TI - TAPBPR mediates peptide dissociation from MHC class I using a leucine lever AU - Ilca, F Tudor AU - Neerincx, Andreas AU - Hermann, Clemens AU - Marcu, Ana AU - Stevanović, Stefan AU - Deane, Janet E AU - Boyle, Louise H A2 - Nussenzweig, Michel C A2 - Wucherpfennig, Kai A2 - Shastri, Nilabh A2 - Van Endert, Peter VL - 7 PY - 2018 DA - 2018/11/28 SP - e40126 C1 - eLife 2018;7:e40126 DO - 10.7554/eLife.40126 UR - https://doi.org/10.7554/eLife.40126 AB - 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-mediated 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 on 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. KW - antigen processing KW - antigen presentation KW - major histocompatibility complex KW - TAPBPR/TAPBPL JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -