TAPBPR mediates peptide dissociation from MHC class I using a leucine lever

eLife

Janet E Deane¹  Louise H Boyle²  Ana Marcu³  Stefan Stevanović³  Clemens Hermann⁴  F Tudor Ilca⁵  Andreas Neerincx⁵ 

[1] DKFZ Partner Site Tübingen, German Cancer Consortium, Tübingen, Germany;Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom;Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany;Department of Integrative Biomedical Sciences, Division of Chemical and Systems Biology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa;Department of Pathology, University of Cambridge, Cambridge, United Kingdom;

关键词: antigen processing;    antigen presentation;    major histocompatibility complex;    TAPBPR/TAPBPL;   

DOI  :  10.7554/eLife.40126

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown