PMID- 33372950
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 180
IP  - 1
DP  - 2021 Feb 26
TI  - Characterization of the Class I MHC Peptidome Resulting From DNCB Exposure of 
      HaCaT Cells.
PG  - 136-147
LID - 10.1093/toxsci/kfaa184 [doi]
AB  - 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 proteome leading to 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 the 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-omega. 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.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Society of Toxicology.
FAU - Bailey, Alistair
AU  - Bailey A
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, University of Southampton, Southampton SO17 1BJ, UK.
AD  - Centre for Cancer Immunology and Institute for Life Sciences, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Nicholas, Ben
AU  - Nicholas B
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, University of Southampton, Southampton SO17 1BJ, UK.
AD  - Centre for Cancer Immunology and Institute for Life Sciences, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Darley, Rachel
AU  - Darley R
AD  - Centre for Cancer Immunology and Institute for Life Sciences, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Parkinson, Erika
AU  - Parkinson E
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, University of Southampton, Southampton SO17 1BJ, UK.
FAU - Teo, Ying
AU  - Teo Y
AD  - Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Aleksic, Maja
AU  - Aleksic M
AD  - Safety & Environmental Assurance Centre, Unilever, Colworth Science Park, 
      Sharnbrook MK44 1LQ, UK.
FAU - Maxwell, Gavin
AU  - Maxwell G
AD  - Safety & Environmental Assurance Centre, Unilever, Colworth Science Park, 
      Sharnbrook MK44 1LQ, UK.
FAU - Elliott, Tim
AU  - Elliott T
AD  - Centre for Cancer Immunology and Institute for Life Sciences, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Ardern-Jones, Michael
AU  - Ardern-Jones M
AD  - Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, Faculty of 
      Medicine, University of Southampton, Southampton SO16 6YD, UK.
FAU - Skipp, Paul
AU  - Skipp P
AD  - Centre for Proteomic Research, Biological Sciences and Institute for Life 
      Sciences, University of Southampton, Southampton SO17 1BJ, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Haptens)
SB  - IM
MH  - *Dinitrochlorobenzene
MH  - *HaCaT Cells
MH  - Haptens/toxicity
MH  - Humans
MH  - Proteomics
MH  - T-Lymphocytes, Cytotoxic
PMC - PMC7916740
OTO - NOTNLM
OT  - DNCB
OT  - HLA
OT  - HaCaT
OT  - keratinocyte
OT  - peptidome
EDAT- 2020/12/30 06:00
MHDA- 2021/08/19 06:00
PMCR- 2020/12/29
CRDT- 2020/12/29 12:09
PHST- 2020/12/30 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/12/29 12:09 [entrez]
PHST- 2020/12/29 00:00 [pmc-release]
AID - 6054830 [pii]
AID - kfaa184 [pii]
AID - 10.1093/toxsci/kfaa184 [doi]
PST - ppublish
SO  - Toxicol Sci. 2021 Feb 26;180(1):136-147. doi: 10.1093/toxsci/kfaa184.