H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cytokines.
H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and interferon (IFN)-gamma in different antigen-presenting cells (APCs). In nonprofessional APCs, e.g., L929 fibroblasts, IFN-gamma-inducible expression of the MHC class II-specific transcription factor CIITA is associated with coordinate expression of MHCII, Ii, H2-M, and H2-Oa genes but without concomitant H2-Ob induction. In contrast, professional APCs, e.g., the macrophage cell line P388D1, exhibit constitutive H2-Oa and H2-Ob expression, which is not inducible by IFN-gamma in contrast to CIITA, MHCII, Ii, and H2-M expression. In B cells, CIITA, MHCII, Ii, and H2-M genes are differentially expressed relative to H2-Oa and H2-Ob genes upon stimulation with IL-4, IL-10, or IFN-gamma. A differential ratio of H2-M to H2-O may represent one mechanism by which professional and nonprofessional APCs bypass H2-O inhibitory activity.
Walter
W
W
Department of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
Scheuer
C
C
Lingnau
K
K
Reichert
T E
TE
Schmitt
E
E
Loos
M
M
Maeurer
M J
MJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D009687:Nuclear Proteins; D010455:Peptides / Q000276:immunology; D012333:RNA, Messenger; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; C416186:H-2O antigen; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D010455:Peptides; D012333:RNA, Messenger; D015534:Trans-Activators; C045084:invariant chain; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma