title: Unraveling features of the natural MHC class II peptidome of skin-migrated dendritic cells.
abstract: 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.
authors.affiliation: Immunology Unit, Institut de Biotecnologia i Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Muixí
authors.forename: Vanessa
authors.initials: V
authors.lastname: Contreras
authors.forename: Javier A
authors.initials: JA
authors.lastname: Collado
authors.forename: Yannick
authors.initials: Y
authors.lastname: Alexandre
authors.forename: Keith
authors.initials: K
authors.lastname: Ballingall
authors.forename: Michel
authors.initials: M
authors.lastname: Bonneau
authors.forename: Dolores
authors.initials: D
authors.lastname: Jaraquemada
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schwartz-Cornil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008196:Lymph / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics; D012756:Sheep; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides