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 tha t catalyzes peptide binding to MHC class II molecules. Recently, the H2-O h eterodimer, encoded by H2-Oa and N2-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 or gans revealed that H2-Oa- and H2-Ob-specific transcripts are present in bot h lymphoid and nonlymphoid tissues. To evaluate the gene regulation and fun ctional impact of H2-O on antigen presentation, we examined the effects on MNCII. invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and interferon (IFN)-gamma in different antigen-presenting c ells (APCs). In nonprofessional APCs, e.g,, L929 fibroblasts, IFN-gamma-ind ucible expression of the MHC class II-specific transcription factor CIITA i s 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 CITTA, 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 stimulatio n 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 bypa ss H2-O inhibitory activity.