title: Differential expression of alternative H2-M isoforms in B cells, dendritic cells and macrophages by proinflammatory cytokines.
abstract: Major histocompatibility (MHC) class II heterodimers bind peptides generated by degradation of endocytosed antigens and display them on the surface of antigen presenting cells (APCs) for recognition by CD4+ T cells. Efficient loading of MHC class II molecules with peptides is catalyzed by the MHC class II-like molecule H2-M. The coordinate regulation of MHC class II and H2-M expression is a prerequisite for efficient MHC class II/peptide assembly in APCs determining both the generation of the T cell repertoire in the thymus and cellular immune responses in the periphery. Here we show that expression of H2-M and MHC class II genes is coordinately and cell type-specific regulated in splenic B cells, splenic dendritic cells (DCs) and peritoneal macrophages (Mphi) in response to proinflammatory and immunoregulatory cytokines, including GM-CSF, IFN-gamma, TGF-beta2, IL-4, IL-10 and viral IL-10. In addition, ratio-RT-PCR expression analysis of the duplicated H2-Mbeta-chain loci demonstrates for the first time that Mbl and Mb2 genes are differentially expressed in individual APC types. Mb2 is preferentially expressed in IL-4, GM-CSF, IL-10, vIL-10 and IFN-gamma stimulated splenic B cells, whereas splenic DCs express both Mb genes at almost equal levels. In contrast, peritoneal Mphi express predominantly Mb2 but stimulation with IFN-gamma induces a switch towards Mb1 expression. These data suggest a common mechanism that regulates coordinate expression of H2-M and MHC class II genes in professional APCs. Differential expression of Mb1 and Mb2, and by consequence alternative H2-M isoforms (Malphabeta1 or Malphabeta2), may influence the nature of the peptide repertoire presented by different APC types.
authors.affiliation: Department of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Walter
authors.forename: M
authors.initials: M
authors.lastname: Loos
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D020033:Protein Isoforms