Tapasin-related protein restricts the MHC class I peptide repertoire by enhancing peptide exchange

Hermann, Clemens, van Hateren, Andy, Trautwein, Nico, Deane, Janet, Elliott, Tim and Boyle, Louise (2015) Tapasin-related protein restricts the MHC class I peptide repertoire by enhancing peptide exchange. Molecular Immunology, 68 (2), 145-146.

Abstract

Recently we have found the tapasin-related protein TAPBPR is an additional MHC I chaperone of unknown function in the antigen presentation system. In contrast to tapasin, TAPBPR is not an integral component of the peptide loading complex and is not required for peptide loading. Furthermore, we have found TAPBPR and tapasin bind in a similar orientation to the same face of MHC I.This raised the possibility that, like tapasin, TAPBPR could functionas an MHC I peptide “editor”.Here we demonstrate that TAPBPR expression has a significanteffect in shaping the peptide repertoire presented by MHC I. Usingin vitro peptide exchange assays we demonstrate that TAPBPRis able to increase peptide association and peptide dissociationfor both HLA-A*02 and -B*08. Therefore, like tapasin, TAPBPR enhances peptide exchange on MHC I. Interestingly, the luminal portion of TAPBPR alone, without the need for a leucine zipper,is sufficient to promote MHC I peptide exchange, suggesting that TAPBPR might have a higher affinity for MHC I than tapasin. Todetermine the in vivo effect of TAPBPR expression on the MHC Ipeptidome, we isolated pMHC I from WT and TAPBPR knockout cells, eluted the bound peptides and determined their amino acid sequence by mass spectrometry. This revealed a significantly broader repertoire of peptides presented on MHC I in the absence of TAPBPR (up to a 9.5 fold increase in the total number of pMHC), despite the fact that cell surface levels of MHC I were unaffected byTAPBPR depletion. This is in contrast to tapasin depletion where a significant decrease in the total number of pMHC was observed.

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Contributors

Author: Andy van Hateren

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