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

Tapasin-related protein restricts the MHC class I peptide repertoire by enhancing peptide exchange
Tapasin-related protein restricts the MHC class I peptide repertoire by enhancing peptide exchange
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.
0161-5890
145-146
Hermann, Clemens
978cedee-4017-43e9-86a7-4665636ce553
van Hateren, Andy
e345fa3c-d89c-4b91-947e-c1d818cc7f71
Trautwein, Nico
2387bf8d-9384-4edb-93e7-3cefe5021ae7
Deane, Janet
dd93a448-fe81-4c8b-884e-a396ada0cebd
Elliott, Tim
8e43fe0d-c251-4ee8-80fa-bcffc8c7e153
Boyle, Louise
e2afc84e-3524-417d-a54b-4f7f7d753866
Hermann, Clemens
978cedee-4017-43e9-86a7-4665636ce553
van Hateren, Andy
e345fa3c-d89c-4b91-947e-c1d818cc7f71
Trautwein, Nico
2387bf8d-9384-4edb-93e7-3cefe5021ae7
Deane, Janet
dd93a448-fe81-4c8b-884e-a396ada0cebd
Elliott, Tim
8e43fe0d-c251-4ee8-80fa-bcffc8c7e153
Boyle, Louise
e2afc84e-3524-417d-a54b-4f7f7d753866

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.

Record type: Meeting abstract

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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Published date: December 2015

Identifiers

Local EPrints ID: 443691
URI: http://eprints.soton.ac.uk/id/eprint/443691
ISSN: 0161-5890
PURE UUID: a620eecd-8a47-43aa-9be0-c0a8f2f56ba7
ORCID for Andy van Hateren: ORCID iD orcid.org/0000-0002-3915-0239

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Date deposited: 09 Sep 2020 16:30
Last modified: 17 Mar 2024 03:08

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Contributors

Author: Clemens Hermann
Author: Nico Trautwein
Author: Janet Deane
Author: Tim Elliott
Author: Louise Boyle

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