PMID- 27529174
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20240210
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - Allele-Independent Turnover of Human Leukocyte Antigen (HLA) Class Ia Molecules.
PG  - e0161011
LID - 10.1371/journal.pone.0161011 [doi]
LID - e0161011
AB  - Major histocompatibility complex class I (MHCI) glycoproteins present cytosolic 
      peptides to CD8+ T cells and regulate NK cell activity. Their heavy chains (HC) 
      are expressed from up to three MHC gene loci (human leukocyte antigen [HLA]-A, 
      -B, and -C in humans), whose extensive polymorphism maps predominantly to the 
      antigen-binding groove, diversifying the bound peptide repertoire. Codominant 
      expression of MHCI alleles is thus functionally critical, but how it is regulated 
      is not fully understood. Here, we have examined the effect of polymorphism on the 
      turnover rates of MHCI molecules in cell lines with functional MHCI peptide 
      loading pathways and in monocyte-derived dendritic cells (MoDCs). Proteins were 
      labeled biosynthetically with heavy water (2H2O), folded MHCI molecules 
      immunoprecipitated, and tryptic digests analysed by mass spectrometry. 
      MHCI-derived peptides were assigned to specific alleles and isotypes, and 
      turnover rates quantified by 2H incorporation, after correcting for cell growth. 
      MHCI turnover half-lives ranged from undetectable to a few hours, depending on 
      cell type, activation state, donor, and MHCI isotype. However, in all settings, 
      the turnover half-lives of alleles of the same isotype were similar. Thus, MHCI 
      protein turnover rates appear to be allele-independent in normal human cells. We 
      propose that this is an important feature enabling the normal function and 
      codominant expression of MHCI alleles.
FAU - Prevosto, Claudia
AU  - Prevosto C
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
FAU - Usmani, M Farooq
AU  - Usmani MF
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
FAU - McDonald, Sarah
AU  - McDonald S
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
FAU - Gumienny, Aleksandra M
AU  - Gumienny AM
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
FAU - Key, Tim
AU  - Key T
AD  - Tissue Typing Laboratory, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Goodman, Reyna S
AU  - Goodman RS
AD  - Tissue Typing Laboratory, Addenbrooke's Hospital, Cambridge, United Kingdom.
FAU - Gaston, J S Hill
AU  - Gaston JS
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
FAU - Deery, Michael J
AU  - Deery MJ
AD  - Cambridge Centre for Proteomics, University of Cambridge, Cambridge, United 
      Kingdom.
FAU - Busch, Robert
AU  - Busch R
AD  - Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
AD  - Department of Life Sciences, University of Roehampton, London, United Kingdom.
LA  - eng
GR  - 16491/CRUK_/Cancer Research UK/United Kingdom
GR  - 18543/VAC_/Versus Arthritis/United Kingdom
GR  - 20648/ARC_/Arthritis Research UK/United Kingdom
GR  - 20648/VAC_/Versus Arthritis/United Kingdom
PT  - Journal Article
DEP - 20160816
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA Antigens)
RN  - J65BV539M3 (Deuterium Oxide)
SB  - IM
MH  - *Alleles
MH  - Cell Line, Tumor
MH  - Deuterium Oxide/chemistry
MH  - HLA Antigens/chemistry/*genetics/*metabolism
MH  - Humans
MH  - Isotope Labeling
PMC - PMC4987023
COIS- Competing Interests: The authors have read the journal's policy and the authors 
      of this manuscript have the following competing interests: RB owns stock in 
      KineMed, Inc., Emeryville, CA, USA, a biopharmaceutical company with intellectual 
      property related to heavy water labeling. This does not alter the authors' 
      adherence to PLOS ONE policies on sharing data and materials.
EDAT- 2016/08/17 06:00
MHDA- 2017/08/02 06:00
PMCR- 2016/08/16
CRDT- 2016/08/17 06:00
PHST- 2016/02/29 00:00 [received]
PHST- 2016/07/28 00:00 [accepted]
PHST- 2016/08/17 06:00 [entrez]
PHST- 2016/08/17 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2016/08/16 00:00 [pmc-release]
AID - PONE-D-16-08688 [pii]
AID - 10.1371/journal.pone.0161011 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 16;11(8):e0161011. doi: 10.1371/journal.pone.0161011. 
      eCollection 2016.