Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026936 (Mycoplasma)
 14,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superantigens are defined as proteins that activate a large number of T cells through interaction with the Vbeta region of the T cell antigen receptor (TCR). Here we demonstrate that the superantigen produced by Mycoplasma arthritidis (MAM), unlike six bacterial superantigens tested, interacts not only with the Vbeta region but also with the CDR3 (third complementarity-determining region) of TCR-beta. Although MAM shares typical features with other superantigens, direct interaction with CDR3-beta is a feature of nominal peptide antigens situated in the antigen groove of major histocompatibility complex (MHC) molecules rather than superantigens. During peptide recognition, Vbeta and Valpha domains of the TCR form contacts with MHC and the complex is stabilized by CDR3-peptide interactions. Similarly, recognition of MAM is Vbeta-dependent and is apparently stabilized by direct contacts with the CDR3-beta region. Thus, MAM represents a new type of ligand for TCR, distinct from both conventional peptide antigens and other known superantigens.
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PMID:Mycoplasma superantigen is a CDR3-dependent ligand for the T cell antigen receptor. 944 12

Superantigens bind to major histocompatibility complex (MHC) class II molecules on antigen presenting cells and T cells in a V beta-restricted manner. Both cell types are activated resulting in cytokine production. Although the MHC-II binding site for superantigens has been well described, little is known as to whether this binding complex has an influence on cytokine induction. In order to assess superantigen induced cytokine production and its correlation to HLA-DR types, the authors stimulated peripheral blood from 40 subjects with superantigens toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin C-3 (SEC-3) and Mycoplasma arthritidis-derived superantigen (MAS), and measured cytokine levels thereafter. The HLA-DR type was determined in each subject. A statistical evaluation was carried out between the highest superantigen cytokine induction and the presence of certain HLA-DR types. Whereas MAS presented a statistical association between the highest cytokine production with HLA-DR4, DR7 and DR12, no such associations were observed for TSST-1 and SEC-3. These results demonstrate that T cell stimulation, and consequently its cytokine production by MAS but not by TSST-1 and SEC-3, depends on the presenting HLA-DR type. Because the diverse HLA-DR specificities are given according to the variability of the beta chain of the HLA-DR molecule, the data suggest the participation of the human MHC-II beta chain in the MAS/MHC-II binding.
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PMID:Cytokine induction by Mycoplasma arthritidis-derived superantigen (MAS), but not by TSST-1 or SEC-3, is correlated to certain HLA-DR types. 946 57

Mycoplasma fermentans incognitus has been isolated from human tissue in patients both with and without AIDS who died of systemic infection. M. fermentans incognitus and other strains of M. fermentans have been associated with rheumatoid arthritis. While cell extracts of M. fermentans incognitus can induce changes in murine and human cells of the monocytic lineage, little is known about interactions of viable organisms with such cells. Because of the central role of macrophages in chronic inflammation, we examined the effects of M. fermentans incognitus on surface markers and functions of THP-1 cells, a well-characterized human monocytic cell line. This cell line has been used extensively in studies of macrophage differentiation, especially following exposure to phorbol esters. Changes in cell morphology, phagocytosis, rate of cell division, and selected surface markers were evaluated in cultures of THP-1 cells exposed to phorbol myristate acetate (PMA), M. fermentans incognitus, or both. As reported by other investigators, PMA induced THP-1 cells to differentiate into cells resembling tissue macrophages. M. fermentans incognitus only minimally affected changes induced by PMA, slightly increasing the percentage of cells positive for FCgammaRI and major histocompatibility complex (MHC) class II antigens. M. fermentans incognitus alone induced an incomplete arrest in the cell cycle at G0 phase, increased phagocytic ability, and enhanced expression of FCgammaRI, CR3, CR4, and MHC class II antigens.
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PMID:Effects of Mycoplasma fermentans incognitus on differentiation of THP-1 cells. 1037 89

Mycoplasma pulmonis infection in rodents causes a chronic inflammatory airway disease with a strong immunological component, leading to mucosal remodeling and angiogenesis. We sought to determine the effect of this infection on the shape and number of dendritic cells and other major histocompatibility complex (MHC) class II expressing cells in the airway mucosa of Wistar rats. Changes in the shape of subepithelial OX6 (anti-MHC class II)-immunoreactive cells were evident in the tracheal mucosa 2 days after intranasal inoculation with M. pulmonis. By 1 week, the shape of the cells had changed from stellate to rounded (mean shape index increased from 0.42 to 0.77). The number of OX6-positive cells was increased 6-fold at 1 week and 16-fold at 4 weeks. Coincident with these changes, many columnar epithelial cells developed OX6 immunoreactivity, which was still present at 4 weeks. We conclude that M. pulmonis infection creates a potent immunologic stimulus that augments and transforms the OX6-immunoreactive cell population in the airways by changing the functional state of airway dendritic cells, initiating an influx of MHC class II expressing cells, and activating expression of MHC class II molecules by airway epithelial cells.
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PMID:Rapid changes in shape and number of MHC class II expressing cells in rat airways after Mycoplasma pulmonis infection. 1265 45

Zinc-dependent superantigens can be divided into two subfamilies based on how they use zinc ions for interactions with major histocompatibility complex (MHC) class II molecules. Members of the first subfamily use zinc ions for interactions with histidine 81 on the beta-chain of MHC class II molecules, whereas members of the second subfamily use zinc ions for dimer formation. The zinc-binding motif is located in the C terminus of the molecule in both subfamilies. While our recent studies with Mycoplasma arthritidis-derived mitogen (MAM) have provided the first direct evidence demonstrating the binding to MHC class II molecules in a zinc-dependent manner, it still not known how zinc coordinates the interaction. Data presented here show that the zinc ion is mainly required to induce MAM/MAM dimer formation. Residues in the N terminus of MAM are involved in dimer formation and MHC class II binding, while histidine 14 and aspartic acid 31 of the MAM sequence are the major residues mediating MAM/MAM dimerization. Zinc-induced dimer formation is necessary for MAM binding, MHC class II-induced cell-cell adhesion, and efficient T cell activation. Together these results depict the unique mode of interaction of MAM in comparison with other superantigens.
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PMID:Zinc-binding sites in the N terminus of Mycoplasma arthritidis-derived mitogen permit the dimer formation required for high affinity binding to HLA-DR and for T cell activation. 1267 30

Mycoplasma arthritidis-derived mitogen (MAM), a bacterial superantigen, has been crystallized in complex with its human receptor, major histocompatibility complex (MHC) class II antigen, by the hanging-drop vapor-diffusion method. Crystals were obtained under three conditions, with ammonium sulfate, phosphate salt and PEG 8000 as the precipitant. The crystals grown under these conditions all belong to space group I222, with the same unit-cell parameters: a = 137.4, b = 178.2, c = 179.6 A. Diffraction data were collected to 3.3 and 3.4 A resolution from crystals of native and selenomethionylated MAM-MHC complexes, respectively. Self- and cross-rotation function calculations suggest the presence of two complex molecules in the asymmetric unit, resulting in a V(M) of 4.0 and a solvent content of 69%. An interpretable electron-density map was produced using a combination of molecular replacement and SAD phasing.
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PMID:Crystallization and preliminary crystallographic analysis of Mycoplasma arthritidis-derived mitogen complexed with peptide/MHC class II antigen. 1474 23

Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing particular TCR Vbeta elements. Here we report the crystal structure of MAM complexed with a major histocompatibility complex (MHC) antigen, HLA-DR1, loaded with haemagglutinin peptide 306-318 (HA). The structure reveals that MAM has a novel fold composed of two alpha-helical domains. This fold is entirely different from that of the pyrogenic superantigens, consisting of a beta-grasped motif and a beta barrel. In the complex, the N-terminal domain of MAM binds orthogonally to the MHC alpha1 domain and the bound HA peptide, and to a lesser extent to the MHC beta1 domain. Two MAM molecules form an asymmetric dimer and cross-link two MHC antigens to form a plausible, dimerized MAM-MHC complex. These data provide the first crystallographic evidence that superantigens can dimerize MHC molecules. Based on our structure, a model of the TCR2MAM2MHC2 complex is proposed.
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PMID:Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex. 1496 88

Dimerization of class II major histocompatibility complex (MHC) plays an important role in the MHC biological function. Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing specific T cell receptor Vbeta elements. Here we have used structural, sedimentation, and surface plasmon resonance detection approaches to investigate the molecular interactions between MAM and the class II MHC molecule HLA-DR1 in the context of a hemagglutinin peptide-(306-318) (HA). Our results revealed that zinc ion can efficiently induce the dimerization of the HLA-DR1/HA complex. Because the crystal structure of the MAM/HLA-DR1/hemagglutinin complex in the presence of EDTA is nearly identical to the structure of the complex crystallized in the presence of zinc ion, Zn(2+) is evidently not directly involved in the binding between MAM and HLA-DR1. Sedimentation and surface plasmon resonance studies further revealed that MAM binds the HLA-DR1/HA complex with high affinity in a 1:1 stoichiometry, in the absence of Zn(2+). However, in the presence of Zn(2+), a dimerized MAM/HLA-DR1/HA complex can arise through the Zn(2+)-induced DR1 dimer. In the presence of Zn(2+), cooperative binding of MAM to the DR1 dimer was also observed.
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PMID:Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen. 1716 41

The amino terminal sequence of the Candida albicans cell wall protein Int1 exhibited partial identity with the major histocompatibility complex (MHC) class II binding site of the Mycoplasma arthritidis superantigen MAM. Int1-positive C. albicans blastospores activated human T lymphocytes and expanded Vbeta subsets 2, 3, and/or 14; Int1-negative strains were inactive. Release of interferon-gamma (IFN-gamma) but not of tumor necrosis factor-alpha or interleukin-6 was Int1 dependent; interleukin-4 and interleukin-10 were not detected. T lymphocyte activation, Vbeta expansion, and IFN-gamma release were associated with a soluble polypeptide that encompassed the first 263 amino acids of Int1 (Pep(263)). Monoclonal antibody 163.5, which recognizes an Int1 epitope that overlaps the region of identity with MAM, significantly inhibited these activities when triggered by Int1-positive blastospores or Pep(263) but not by staphylococcal enterotoxin B. Histidine(263) was required. Pep(263) bound to T lymphocytes and MHC class II and was detected in the urine of a patient with C. albicans fungemia. These studies identify a candidal protein that displays superantigen-like activities.
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PMID:Superantigen-like effects of a Candida albicans polypeptide. 1841 34

Pulmonary inflammation often results in expression of the class II major histocompatibility complex (MHCII) by both professional antigen-presenting cells (APCs; histiocytes and lymphocytes) and non-professional APCs (respiratory epithelium and endothelium). In this study lesions from 17 cases of bovine chronic pneumonia, associated with Mycoplasma bovis infection, were examined immunohistochemically for M. bovis antigen and MHCII expression. Ten cases of chronic necrosuppurative bronchopneumonia (NBP) were shown to be characterized by abundant perinecrotic M. bovis antigen associated with scant MHCII expression by degenerate leucocytes. Seven cases of chronic catarrhal bronchointerstitial pneumonia (CBP) showed prominent MHCII expression by both professional APCs and respiratory epithelium, in the absence of intralesional M. bovis immunolabelling. The results suggest that prominent MHCII expression by both professional and non-professional APCs plays a role in the pathogenesis of M. bovis-induced CBP. Conversely, the role of MHCII expression in necrosuppurative foci typical of M. bovis-associated NBP can be considered negligible.
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PMID:Expression of class II major histocompatibility complex molecules in chronic pulmonary Mycoplasma bovis infection in cattle. 1913 12


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