Proteomics

Dataset Information

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Identification of sensitiser modified HLA-peptides presented by keratinocytes


ABSTRACT: Skin sensitisation 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 are three nonmutually exclusive models 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 address the mechanism in skin, we set out to utilise 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 provide support for the hypothesis that a key mechanism of skin sensitisation is stimulation of CTLs by haptenated peptides.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Keratinocyte

DISEASE(S): Disease Free

SUBMITTER: Alistair Bailey  

LAB HEAD: Paul J Skipp

PROVIDER: PXD021373 | Pride | 2021-01-04

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20170518_SPhs_validated.fasta Fasta
AB_240220_P1_AETEC_10ng_001.mgf Mgf
AB_240220_P1_AETEC_10ng_001.raw Raw
AB_240220_P2_RFCPF_10ng_001.mgf Mgf
AB_240220_P2_RFCPF_10ng_001.raw Raw
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Publications

Characterization of the Class I MHC Peptidome Resulting From DNCB Exposure of HaCaT Cells.

Bailey Alistair A   Nicholas Ben B   Darley Rachel R   Parkinson Erika E   Teo Ying Y   Aleksic Maja M   Maxwell Gavin G   Elliott Tim T   Ardern-Jones Michael M   Skipp Paul P  

Toxicological sciences : an official journal of the Society of Toxicology 20210201 1


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 (HLA) molecules presented on the surface of almost all nucleated cells. There exist 3 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 proteo  ...[more]

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