title: TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst.
abstract: Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC class I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Clemens
authors.identifier: http://orcid.org/0000-0002-0009-9501
authors.initials: C
authors.lastname: Hermann
authors.affiliation: Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom.
authors.forename: Andy
authors.identifier: http://orcid.org/0000-0002-3915-0239
authors.initials: A
authors.lastname: van Hateren
authors.affiliation: Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Nico
authors.identifier: http://orcid.org/0000-0003-3292-8850
authors.initials: N
authors.lastname: Trautwein
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andreas
authors.identifier: http://orcid.org/0000-0002-6902-5383
authors.initials: A
authors.lastname: Neerincx
authors.affiliation: Cancer Research UK Protein Core Facility, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Patrick J
authors.identifier: http://orcid.org/0000-0003-1814-2552
authors.initials: PJ
authors.lastname: Duriez
authors.affiliation: Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0003-1954-7762
authors.initials: S
authors.lastname: Stevanović
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: John
authors.identifier: http://orcid.org/0000-0002-0150-5698
authors.initials: J
authors.lastname: Trowsdale
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Janet E
authors.identifier: http://orcid.org/0000-0002-4863-0330
authors.initials: JE
authors.lastname: Deane
authors.affiliation: Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom.
authors.forename: Tim
authors.identifier: http://orcid.org/0000-0003-1097-0222
authors.initials: T
authors.lastname: Elliott
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Louise H
authors.identifier: http://orcid.org/0000-0002-3105-6555
authors.initials: LH
authors.lastname: Boyle
mesh_terms: D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000941:Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008565:Membrane Proteins; D010455:Peptides; C454688:TAPBPL protein, human
keywords: MHC; antigen processing and presentation; cell biology; human; immunology; peptide repertoire