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Characterization of the class I MHC peptidome resulting from DNCB exposure of HaCaT cells

Characterization of the class I MHC peptidome resulting from DNCB exposure of HaCaT cells
Characterization of the class I MHC peptidome resulting from DNCB exposure of HaCaT cells

Skin sensitization following the covalent modification of proteins by low molecular weight chemicals (haptenation) is mediated by cytotoxic T lymphocyte (CTL) recognition of human leukocyte antigen molecules (HLA) presented on the surface of almost all nucleated cells. There exists three nonmutually exclusive hypotheses for how haptens mediate CTL recognition: direct stimulation by haptenated peptides; hapten modification of HLA leading to an altered HLA-peptide repertoire; or a hapten altered proteome leading to an an altered HLA-peptide repertoire. To shed light on the mechanism underpinning skin sensitization, we set out to utilize proteomic analysis of keratinocyte presented antigens following exposure to 2,4-dinitrochlorobenzene (DNCB). We show that following DNCB exposure, cultured keratinocytes present cysteine haptenated (dinitrophenylated) peptides in multiple HLA molecules. In addition, we find that one of the DNCB modified peptides derives from the active site of cytosolic glutathione-S transferase-ω. These results support the current view that a key mechanism of skin sensitization is stimulation of CTLs by haptenated peptides. Data are available via ProteomeXchange with identifier PXD021373.

1096-6080
Bailey, Alistair
541e2cd9-ac72-4058-9293-def64fc2c284
Nicholas, Benjamin
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Darley, Rachel
840a775a-867e-42ba-a7cb-d131c9fdb9c6
Parkinson, Erika
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Teo, Ying
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Aleksic, Maja
152a8f09-84c2-4ebb-94c7-79c31edf53aa
Maxwell, Gavin
b09b03f9-0c15-4fd3-bee9-e7e0a810b60e
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Bailey, Alistair
541e2cd9-ac72-4058-9293-def64fc2c284
Nicholas, Benjamin
785c44fb-6536-4189-803b-4545425e9385
Darley, Rachel
840a775a-867e-42ba-a7cb-d131c9fdb9c6
Parkinson, Erika
b7294dcc-43d3-46c4-bd19-7f6795b80fe6
Teo, Ying
f3243472-0f73-4bdc-ad4f-2f67247e21c4
Aleksic, Maja
152a8f09-84c2-4ebb-94c7-79c31edf53aa
Maxwell, Gavin
b09b03f9-0c15-4fd3-bee9-e7e0a810b60e
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Ardern-Jones, Michael
7ac43c24-94ab-4d19-ba69-afaa546bec90
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5

Bailey, Alistair, Nicholas, Benjamin, Darley, Rachel, Parkinson, Erika, Teo, Ying, Aleksic, Maja, Maxwell, Gavin, Elliott, Timothy, Ardern-Jones, Michael and Skipp, Paul (2020) Characterization of the class I MHC peptidome resulting from DNCB exposure of HaCaT cells. Toxicological Sciences, [kfaa184]. (doi:10.1093/toxsci/kfaa184).

Record type: Article

Abstract

Skin sensitization following the covalent modification of proteins by low molecular weight chemicals (haptenation) is mediated by cytotoxic T lymphocyte (CTL) recognition of human leukocyte antigen molecules (HLA) presented on the surface of almost all nucleated cells. There exists three nonmutually exclusive hypotheses for how haptens mediate CTL recognition: direct stimulation by haptenated peptides; hapten modification of HLA leading to an altered HLA-peptide repertoire; or a hapten altered proteome leading to an an altered HLA-peptide repertoire. To shed light on the mechanism underpinning skin sensitization, we set out to utilize proteomic analysis of keratinocyte presented antigens following exposure to 2,4-dinitrochlorobenzene (DNCB). We show that following DNCB exposure, cultured keratinocytes present cysteine haptenated (dinitrophenylated) peptides in multiple HLA molecules. In addition, we find that one of the DNCB modified peptides derives from the active site of cytosolic glutathione-S transferase-ω. These results support the current view that a key mechanism of skin sensitization is stimulation of CTLs by haptenated peptides. Data are available via ProteomeXchange with identifier PXD021373.

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e-pub ahead of print date: 29 December 2020
Additional Information: © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology.

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Local EPrints ID: 445986
URI: http://eprints.soton.ac.uk/id/eprint/445986
ISSN: 1096-6080
PURE UUID: bd94e36b-d77e-4f48-aabc-52861b2d49c2
ORCID for Alistair Bailey: ORCID iD orcid.org/0000-0003-0023-8679
ORCID for Timothy Elliott: ORCID iD orcid.org/0000-0003-1097-0222
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959

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Date deposited: 18 Jan 2021 17:31
Last modified: 18 Feb 2021 17:21

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Contributors

Author: Alistair Bailey ORCID iD
Author: Benjamin Nicholas
Author: Rachel Darley
Author: Erika Parkinson
Author: Ying Teo
Author: Maja Aleksic
Author: Gavin Maxwell
Author: Timothy Elliott ORCID iD
Author: Paul Skipp ORCID iD

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