TAPBPR Mediates Peptide Dissociation from MHC Class I Using a Leucine Lever

Overview

Journal Elife

Specialty Biology

Date 2018 Nov 29

PMID 30484775

Citations 22

Authors

F Tudor Ilca

Andreas Neerincx

Clemens Hermann

Ana Marcu

Stefan Stevanovic

Janet E Deane

Louise H Boyle

Affiliations

Soon will be listed here.

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-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.

Citing Articles

CryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.

Sun Y, Pumroy R, Mallik L, Chaudhuri A, Wang C, Hwang D Proc Natl Acad Sci U S A. 2025; 122(2):e2416992122.

PMID: 39786927 PMC: 11745410. DOI: 10.1073/pnas.2416992122.

Reanalysis of Immunopeptidomics Datasets Provides Mechanistic Insight into TAPBPR-Mediated Peptide Editing on HLA-A, -B and -C Molecules.

Altenburg A, Morley J, Bauer J, Walz J, Boyle L Wellcome Open Res. 2024; 9:113.

PMID: 38800518 PMC: 11126903. DOI: 10.12688/wellcomeopenres.20738.1.

Chaperone-mediated MHC-I peptide exchange in antigen presentation.

Jiang J, Natarajan K, Margulies D IUCrJ. 2024; 11(Pt 3):287-298.

PMID: 38656309 PMC: 11067752. DOI: 10.1107/S2052252524002768.

Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.

Sun Y, Papadaki G, Devlin C, Danon J, Young M, Winters T Sci Adv. 2023; 9(8):eade7151.

PMID: 36827371 PMC: 9956121. DOI: 10.1126/sciadv.ade7151.

Partial peptide dissociation and binding groove plasticity in two major histocompatibility complex class I alleles - differences between alleles force field and sampling effects.

Wingbermuhle S, Schafer L RSC Adv. 2022; 12(46):29908-29914.

PMID: 36321080 PMC: 9580618. DOI: 10.1039/d2ra05324a.

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