PMID- 27365532
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20171212
IS  - 1938-3673 (Electronic)
IS  - 0741-5400 (Linking)
VI  - 101
IP  - 1
DP  - 2017 Jan
TI  - Analysis of the HLA-DR peptidome from human dendritic cells reveals high affinity 
      repertoires and nonconventional pathways of peptide generation.
PG  - 15-27
LID - 10.1189/jlb.6HI0216-069R [doi]
AB  - Dendritic cells (DCs) are the major professional APCs of the immune system; 
      however, their MHC-II-associated peptide repertoires have been hard to analyze, 
      mostly because of their scarce presence in blood and tissues. In vitro matured 
      human monocyte-derived DCs (MoDCs) are widely used as professional APCs in 
      experimental systems. In this work, we have applied mass spectrometry to identify 
      the HLA-DR-associated self-peptide repertoires from small numbers of mature MoDCs 
      ( approximately 5 x 10(6) cells), derived from 7 different donors. Repertoires of 9 different 
      HLA-DR alleles were defined from analysis of 1319 peptides, showing the expected 
      characteristics of MHC-II-associated peptides. Most peptides identified were 
      predicted high binders for their respective allele, formed nested sets, and 
      belonged to endo-lysosomal pathway-degraded proteins. Approximately 20% of the 
      peptides were derived from cytosolic and nuclear proteins, a recurrent finding in 
      HLA-DR peptide repertoires. Of interest, most of these peptides corresponded to 
      single sequences, did not form nested sets, and were located at the C terminus of 
      the parental protein, which suggested alternative processing. Analysis of 
      cleavage patterns for terminal peptides predominantly showed aspartic acid before 
      the cleavage site of both C- and N-terminal peptides and proline immediately 
      after the cleavage site in C-terminal peptides. Proline was also frequent next to 
      the cut sites of internal peptides. These data provide new insights into the Ag 
      processing capabilities of DCs. The relevance of these processing pathways and 
      their contribution to response to infection, tolerance induction, or autoimmunity 
      deserve further analysis.
CI  - (c) Society for Leukocyte Biology.
FAU - Ciudad, M Teresa
AU  - Ciudad MT
AD  - Department of Cell Biology, Physiology and Immunology, Laboratori d'Immunologia 
      Cellular, Institut de Biotecnologia i Biomedicina, Universitat Autonoma de 
      Barcelona, Barcelona, Spain.
FAU - Sorvillo, Nicoletta
AU  - Sorvillo N
AD  - Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The 
      Netherlands.
AD  - Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
FAU - van Alphen, Floris P
AU  - van Alphen FP
AD  - Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The 
      Netherlands.
FAU - Catalan, Diego
AU  - Catalan D
AD  - Programa Disciplinario de Inmunologia, Instituto de Ciencias Biomedicas, Facultad 
      de Medicina, Universidad de Chile, Santiago, Chile; and.
FAU - Meijer, Alexander B
AU  - Meijer AB
AD  - Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The 
      Netherlands.
AD  - The Netherlands and Department of Pharmaceutics, Utrecht Institute for 
      Pharmaceutical Sciences, Utrecht University, The Netherlands.
FAU - Voorberg, Jan
AU  - Voorberg J
AD  - Department of Plasma Proteins, Sanquin-AMC Landsteiner Laboratory, Amsterdam, The 
      Netherlands.
FAU - Jaraquemada, Dolores
AU  - Jaraquemada D
AD  - Department of Cell Biology, Physiology and Immunology, Laboratori d'Immunologia 
      Cellular, Institut de Biotecnologia i Biomedicina, Universitat Autonoma de 
      Barcelona, Barcelona, Spain; dolores.jaraquemada@uab.cat.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160630
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Alleles
MH  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Cell Differentiation
MH  - Cytosol/metabolism
MH  - Databases, Protein
MH  - Dendritic Cells/*metabolism
MH  - Endosomes/metabolism
MH  - HLA-DR Antigens/*metabolism
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Monocytes/cytology
MH  - Nuclear Proteins/metabolism
MH  - Peptide Hydrolases/metabolism
MH  - Peptides/chemistry/*metabolism
MH  - Phenotype
MH  - Proteome/*metabolism
OTO - NOTNLM
OT  - Ag presentation
OT  - Ag processing
OT  - MHC class II
OT  - autologous peptides
OT  - mass spectrometry
EDAT- 2016/07/02 06:00
MHDA- 2017/09/02 06:00
CRDT- 2016/07/02 06:00
PHST- 2016/02/05 00:00 [received]
PHST- 2016/05/24 00:00 [revised]
PHST- 2016/06/12 00:00 [accepted]
PHST- 2016/07/02 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2016/07/02 06:00 [entrez]
AID - jlb.6HI0216-069R [pii]
AID - 10.1189/jlb.6HI0216-069R [doi]
PST - ppublish
SO  - J Leukoc Biol. 2017 Jan;101(1):15-27. doi: 10.1189/jlb.6HI0216-069R. Epub 2016 
      Jun 30.