title: Uncompromised generation of a specific H-2DM-dependent peptide-MHC class II complex from exogenous antigen in Leishmania mexicana-infected dendritic cells.
abstract: Leishmania infection inhibits the capacity of macrophages (MPhi) to present antigens to CD4(+) T cells. Relocation of MHC class II and H-2DM to the parasitophorous vacuole (PV) and their subsequent degradation by the parasite may contribute to this defect. Dendritic cells (DC) are critical for initiation of primary T cell responses. DC can process Leishmania antigen and elicit Leishmania-specific T cells, but it is unknown whether exposure to Leishmania impairs this capacity. In particular, it is not clear whether DC containing live parasites efficiently process and present antigens. We investigated the ability of mouse bone marrow-derived DC infected with L. mexicana to generate pigeon cytochrome c (PCC) peptide-MHC class II complexes, using the mAb D4, which recognizes PCC(89-104) H-2E(k), and the PCC-specific T cell hybridoma 2B4. We show that H-2DM-dependent complex generation is not compromised by infection and that complexes are fully recognized by specific T cells. We further show that in contrast to infected MPhi, in infected DC cytoplasmic H-2DM is not down-regulated and not relocated to the parasite-containing vacuole. This observation may explain the continued ability of infected DC to present PCC, and also indicates differences in the habitat of these intracellular parasites in DC compared to MPhi.
authors.affiliation: Institute for Stem Cell Research and Institute for Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, GB.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Bennett
authors.forename: Lisa
authors.initials: L
authors.lastname: Colledge
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Richards
authors.forename: Philip A
authors.initials: PA
authors.lastname: Reay
authors.forename: C Clare
authors.initials: CC
authors.lastname: Blackburn
authors.forename: Toni
authors.initials: T
authors.lastname: Aebischer
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D010856:Columbidae; D045304:Cytochromes c / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology*; D005260:Female; D006183:H-2 Antigens / Q000378:metabolism* / Q000502:physiology*; D007894:Leishmania mexicana / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA
chemical_list: D006183:H-2 Antigens; C068318:H-2E(k) antigen; D045304:Cytochromes c