Differential expression of alternative H2-M isoforms in B cells, dendriticcells and macrophages by proinflammatory cytokines

Major histocompatibility (MHC) class II heterodimers bind peptides generate d by degradation of endocytosed antigens and display them on the surface of antigen presenting cells (APCs) for recognition by CD4(+) T cells. Efficie nt 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 assemb ly 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 ex pression of H2-M and MHC class II genes is coordinately and cell type-speci fic regulated in splenic B cells, splenic dendritic cells (DCs) and periton eal macrophages (M Phi) in response to proinflammatory and immunoregulatory cytokines, including CM-CSF, IFN-gamma, TGF-beta 2, IL-4, IL-10 and viral IL-10. In addition, ratio-RT-PCR expression analysis of the duplicated H2-M beta-chain loci demonstrates for the first time that Mb1 and Mb2 genes are differentially expressed in individual APC types. Mb2 is preferentially ex pressed in IL-4, GM-CSF, IL-10, vIL-10 and IFN-gamma stimulated splenic B c ells, whereas splenic DCs express both Mb genes at almost equal levels. in contrast, peritoneal M Phi express predominantly Mb2 but stimulation with I FN-gamma induces a switch towards Mb1 expression. These data suggest a comm on 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 (M alpha beta 1 or M alpha beta 2), m ay influence the nature of the peptide repertoire presented by different AP C types. (C) 1999 Elsevier Science Ltd. All rights reserved.