0000000000309090
AUTHOR
Wolfgang Walter
Toxoplasma gondii down-regulates MHC class II gene expression and antigen presentation by murine macrophages via interference with nuclear translocation of STAT1α
The obligate intracellular protozoan parasite Toxoplasma gondii is able to establish persistent infections within human and animal hosts. We have shown recently that T. gondii down-regulates IFN-γ-induced MHC class II expression in murine bone marrow-derived macrophages (BMMΦ). As shown in this study, the capacity of IFN-γ-activated murine BMMΦ to present ovalbumin to CD4+ T cell hybridomas was dose-dependently inhibited by T. gondii. IFN-γ-induced up-regulation of H2-Aa, H2-Ab, H2-Eb, H2-Ma, H2-Mb, H2-Oa and invariant chain transcripts was prominently down-regulated by T. gondii. Furthermore, mRNA levels of class II transactivator and interferon-regulatory factor-1 were significantly dimin…
H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove.
The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibilityI-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequencedH2-Ma, H2-Mb1, andH2-Mb2 genes from CIA-susceptible and-resistant mouse strains and identified four differentMa andMb2 alleles and three differentMb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share commonMa, M…
Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?
alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant V alpha 14 J alpha 281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. …
Differential expression of alternative H2-M isoforms in B cells, dendritic cells and macrophages by proinflammatory cytokines.
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…
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 inter…
Interleukin-7 or Interleukin-15 Enhances Survival ofMycobacterium tuberculosis-Infected Mice
ABSTRACTBoth antigen-presenting cells and immune effector cells are required to effectively eradicate or containMycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive “cross talk” between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of α/β and γ/δ T cells. Here we show that either cytokine is able to enhance survival ofM. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival cou…
H2-Mβ1 and H2-Mβ2 Heterodimers Equally Promote CLIP Removal in I-Aq Molecules from Autoimmune-prone DBA/1 Mice
Antigen-presenting cells degrade endocytosed antigens, e.g. collagen type II, into peptides that are bound and presented to arthritogenic CD4(+) helper T cells by major histocompatibility complex (MHC) class II molecules. Efficient loading of many MHC class II alleles with peptides requires the assistance of H2-M (HLA-DM in humans), a heterodimeric MHC class II-like molecule that facilitates CLIP removal from MHC class II molecules and aids to shape the peptide repertoire presented by MHC class II to CD4(+) T cells. In contrast to the HLA-DM region in humans, the beta-chain locus is duplicated in mice, with the H2-Mb1 beta-chain distal to H2-Mb2 and the H2-Ma alpha-chain gene. H2-M alleles …
Differential expression of the murine mannose-binding lectins A and C in lymphoid and nonlymphoid organs and tissues.
Abstract Mannose-binding lectin (MBL), a member of the collectin family, binds to carbohydrate structures on the surfaces of micro-organisms and may serve as a recognition molecule of the lectin pathway of complement activation. In rodents two forms, MBL-A and MBL-C, were described and shown to be products of two related, but uncoupled, genes. The liver is the main source of MBL biosynthesis. For rat MBL-A, expression has also been described in the kidney. Here we report that the two forms of murine MBL are differentially expressed in a number of nonhepatic tissues. Real-time RT-PCR revealed that the liver is the major site of expression for both MBL genes. Lower copy numbers were found in …