title: Rapid constitutive generation of a specific peptide-MHC class II complex from intact exogenous protein in immature murine dendritic cells.
abstract: MHC class II molecules present peptides, derived largely from exogenous antigens, to CD4+ T cells. Complex-generation occurs mainly in the specialized late endosomal MHC class II-rich compartment (MIIC) vesicles of antigen-presenting cells (APC). Dendritic cells (DC) have been reported to store intact antigen in MIIC until the receipt of an activation signal, when they process it into peptide-MHC class II complexes. However, constitutive migration of DC from the periphery to secondary lymphoid organs has been observed, and antigen presentation by nonactivated DC is proposed to play a role in the induction of tolerance to peripheral antigens. Thus, constitutive peptide-MHC class II complex generation must also occur in DC in immunologically quiescent situations. We have used a monoclonal antibody that detects a specific peptide-MHC class II complex to directly demonstrate constitutive complex generation in immature murine DC. Protein-derived peptide-MHC class II complexes were detected by flow cytometry at the DC surface within 1 h of antigen exposure in the absence of an exogenous activation signal, and could be detected by confocal microscopy in the MIIC within 5 min of antigen exposure. This processing activity was endotoxin independent. These data provide evidence for constitutive peptide-MHC class II complex generation in immature DC, and thus support a role for this activity in the induction of peripheral tolerance.
authors.affiliation: Institute for Stem Cell Research, Institute for Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, GB.
authors.forename: Lisa
authors.initials: L
authors.lastname: Colledge
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Philip A
authors.initials: PA
authors.lastname: Reay
authors.forename: C Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens / Q000378:metabolism; D002478:Cells, Cultured; D010856:Columbidae; D003574:Cytochrome c Group / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007108:Immune Tolerance; D051379:Mice; D008808:Mice, Inbred CBA; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D003574:Cytochrome c Group; D006183:H-2 Antigens; C068318:H-2E(k) antigen; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments