title: Presentation of type B peptide-MHC complexes from hen egg white lysozyme by TLR ligands and type I IFNs independent of H2-DM regulation.
abstract: In APCs, presentation by MHC II molecules of the chemically dominant peptide from the protein hen egg white lysozyme (HEL) generates different conformational isomers of the peptide-MHC II complexes (pMHC). Type B pMHCs are formed in early endosomes from exogenous peptides in the absence of H2-DM, whereas in contrast, type A pMHC complexes are formed from HEL protein in late vesicles after editing by H2-DM. Thus, H2-DM edits off the more unstable pMHC complexes, which are not presented from HEL. In this study, we show that type B pMHC complexes were presented from HEL protein only after stimulation of dendritic cells (DC) with TLR ligands or type I IFN. Type I IFN contributed to most TLR ligand-induced type B pMHC generation, as presentation decreased in DC lacking the receptor for type I IFNs (IFNAR1(-/-)). In contrast, presentation of type A pMHC from HEL and from peptide was minimally affected by TLR ligands. The relative effectiveness of CD8α(+) DC or CD8α(-) DC in presenting type B pMHC complexes varied depending on the TLR ligand used. The mechanisms of generation of type B pMHC from HEL protein with TLR stimulation did not involve H2-DM or release of peptides. DC from H2-DM-deficient mice in the presence of TLR ligands presented type B pMHC. Such DC showed a slight enhancement of HEL catabolism, but peptide release was not evident. Thus, TLR ligands and type I IFN alter the pathways of presentation by MHC II molecules of DC such that type B pMHCs are generated from protein Ag.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Beverly S I
authors.initials: BS
authors.lastname: Strong
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D008024:Ligands; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D008024:Ligands; D051193:Toll-Like Receptors; C421864:hen egg lysozyme; D009113:Muramidase