PMID- 22194283 OWN - NLM STAT- MEDLINE DCOM- 20120511 LR - 20111229 IS - 1460-2377 (Electronic) IS - 0953-8178 (Linking) VI - 24 IP - 1 DP - 2012 Jan TI - Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells. PG - 59-69 LID - 10.1093/intimm/dxr096 [doi] AB - Dendritic cells (DCs) migrating from peripheral tissues at steady state are considered the most efficient antigen-presenting cells (APCs) involved in the induction of peripheral T-cell tolerance via self-antigen presentation on MHC class II molecules. However, difficulties in obtaining sufficient numbers of such DCs have precluded previous analyses of their natural MHC class II peptidome in laboratory animals or humans. Here, we overcome this difficulty by collecting the large quantities of sheep DCs that migrate from the skin via the afferent lymphatics at steady state to the draining lymph node. We compared the repertoire of MHC class II-bound peptides from afferent lymph DCs with autologous APCs derived from peripheral blood. A large fraction of the MHC class II peptidome from skin DCs was derived from membrane-recycling proteins (59%) and from proteins of the antigen presentation machinery (50%), whereas these types of peptides constituted a more limited fraction in blood APCs (21 and 11%, respectively). One sheep cytokeratin peptide was identified in the skin DC peptidome indicating active processing of epithelium-derived antigens. Conversely, peptides derived from cytosolic and soluble antigens of the extracellular milieu were more represented in blood APCs than skin DCs. The biased peptidome of skin-migrated DCs indicates that these cells express a peptide repertoire for the generation of self-reactive and/or regulatory T cells mainly directed toward DC molecules from internal and external membranes and to a lesser extent toward antigens of the extracellular milieu, including some tissue-specific peptides. FAU - Muixi, Laia AU - Muixi L AD - Immunology Unit, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain. FAU - Contreras, Vanessa AU - Contreras V FAU - Collado, Javier A AU - Collado JA FAU - Alexandre, Yannick AU - Alexandre Y FAU - Ballingall, Keith AU - Ballingall K FAU - Bonneau, Michel AU - Bonneau M FAU - Jaraquemada, Dolores AU - Jaraquemada D FAU - Schwartz-Cornil, Isabelle AU - Schwartz-Cornil I LA - eng PT - Journal Article DEP - 20111222 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Autoantigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) SB - IM MH - Amino Acid Sequence MH - Animals MH - Antigen-Presenting Cells/immunology/metabolism MH - Autoantigens/immunology/metabolism MH - Cell Movement/*immunology MH - Chromatography, High Pressure Liquid MH - Dendritic Cells/*immunology/metabolism MH - Female MH - Flow Cytometry MH - Genotype MH - Histocompatibility Antigens Class II/genetics/*immunology/metabolism MH - Leukocytes, Mononuclear/immunology/metabolism MH - Lymph/immunology/metabolism MH - Lymph Nodes/immunology/metabolism MH - Mass Spectrometry MH - Molecular Sequence Data MH - Peptides/*immunology/metabolism MH - Proteomics MH - Sheep MH - Skin/*immunology/metabolism MH - T-Lymphocytes/immunology/metabolism EDAT- 2011/12/24 06:00 MHDA- 2012/05/12 06:00 CRDT- 2011/12/24 06:00 PHST- 2011/12/24 06:00 [entrez] PHST- 2011/12/24 06:00 [pubmed] PHST- 2012/05/12 06:00 [medline] AID - dxr096 [pii] AID - 10.1093/intimm/dxr096 [doi] PST - ppublish SO - Int Immunol. 2012 Jan;24(1):59-69. doi: 10.1093/intimm/dxr096. Epub 2011 Dec 22.