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Query: UMLS:C0026936 (Mycoplasma)
 14,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microbial superantigens (SA) activate a significant portion of the T cell repertoire based on their dual avidity for MHC class II antigens and T cell receptor (TCR) epitopes common to products of one or several TCR beta chain variable gene families. While SA that induce massive T cell proliferation and cytokine secretion have been implicated in clinical syndromes characterized by shock and generalized immunosuppression, SA activation of a more restricted T cell response may also have significant, perhaps immunostimulatory, effects on the immune system. To investigate this issue, we measured 3H-thymidine incorporation and polyclonal IgM and IgG secretion by normal human peripheral blood mononuclear cells (PBMC) cultured with a panel of microbial SA, including the Staphylococcus aureus-derived SA, SEA, SEB, SEC-1, SEC-2, SEC-3, SEE, TSST-1, and the Mycoplasma arthritidis-derived SA, MAM. The S. aureus-derived SA induce vigorous proliferation by PBMC, while optimal MAM-induced proliferation is significantly lower in magnitude. In all 12 subjects tested, mitogenic concentrations of MAM reproducibly stimulate unselected PBMC to secrete polyclonal IgM and IgG. In contrast, the S. aureus-derived SA induce Ig production only in cultures containing isolated B cell populations and either very low numbers of untreated autologous T cells, larger numbers of X-irradiated autologous T cells, or very low concentrations of the SA. No difference in the activation of helper (CD4) versus suppressor/cytotoxic (CD8) T cells by MAM and the S. aureus-derived SA was noted. Taken together, these data suggest that MAM's capacity to induce B cell differentiation correlates with its induction of a relatively weak proliferative response by unselected human T cells. MAM-like SA, when encountered in vivo, may result in a significant perturbation of the human immune system and potentially contribute to clinical syndromes characterized by immunostimulation and hypergammaglobulinemia.
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PMID:Human B cell differentiation induced by microbial superantigens: unselected peripheral blood lymphocytes secrete polyclonal immunoglobulin in response to Mycoplasma arthritidis mitogen. 129 44

The superantigens are receiving a great deal of attention as a new group of potent immunomodulatory molecules. They are produced by diverse microbial agents including staphylococci, streptococci and mycoplasmas and are also encoded by murine tumor viruses (the Mls antigens). Superantigens activate T cells by a unique pathway which can lead to modification of the T-cell repertoire and induction of autoimmunity. Here, Barry Cole and Curtis Atkin review their observations on the Mycoplasma arthritidis superantigen, MAM, and discuss how MAM might contribute to the acute and chronic inflammatory disease mediated by this organism.
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PMID:The Mycoplasma arthritidis T-cell mitogen, MAM: a model superantigen. 191 Apr 49

Mycoplasma arthritidis produces a potent soluble T lymphocyte mitogen (MAM) which is dependent upon accessory cells bearing the alpha-chain of the I-E molecule (E alpha). Lymphocytes from the RIIIS mouse strain which possess E alpha yet whose T cells fail to recognize the MAM-E alpha complex were shown not to express V beta 8.1, 8.2 or 8.3 gene products present on the TCR-alpha/beta by virtue of their lack of reactivity with the F23.1 mAb. Because lymphocytes from the congenic B10.RIII mouse strain reacted positively with F23.1, we examined the progeny from (RIIIS x B10.RIII)F1 x RIIIS backcross mice for cosegregation of lymphocytes expressing F23.1-reactive sites and ability to proliferate in response to MAM. Whereas lymphocytes of all mice responded to Con A, only lymphocytes from progeny expressing F23.1-reactive cells responded to MAM. Similar studies were conducted on progeny from the F23.1- SWR mouse which was backcrossed to (SWR x B10.RIII)F1 mice. Of the E alpha-bearing progeny, there was a direct correlation between lymphocyte expression of F23.1 determinants and ability to respond to MAM. These results established that MAM reactivity was dependent upon a product(s) of the V beta locus of the TCR-alpha/beta. Nodal and thymic lymphocytes cultured for 3 days in vitro with MAM exhibited clonal expansion of F23.1 and F23.2-reactive cells as compared with cultures treated with Con A. We also demonstrated that F23.1 and F23.2 mAb inhibited the ability of lymphocytes to proliferate in response to MAM but had little effect on responses to Con A. The combined data suggest that the MAM-E alpha complex can utilize a V beta 8 gene product(s) on the TCR-alpha/beta.
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PMID:Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. VII. Responsiveness is associated with expression of a product(s) of the V beta 8 gene family present on the T cell receptor alpha/beta for antigen. 278 24

Previous studies established that Mycoplasma arthritidis produces a soluble T cell mitogen (MAM), and that response of murine T cells to MAM is genetically restricted. MAM appeared predominantly in the supernatants of senescent cultures, but was not extracted in significant amounts from whole cells. A quantitative assay of MAM activity was devised. MAM formed noncovalent complexes with nucleic acids and uncharacterized high m.w. constituents of sera and of complex media. Partially purified MAM was adsorbed or denatured by glass and plastic surfaces. MAM was protease-labile, had pI greater than or equal to 9, and had Mr ca 15,000 according to gel filtration experiments. MAM was a very minor component of culture supernatant proteins, and even after 200- to estimated 5 X 10(4)-fold purification was not identified as a stainable or ultraviolet-absorbing entity in electrophoretigrams or chromatograms. It was estimated that MAM was half-optimally active at less than 1000th the half-optimal concentration of concanavalin A or phytohemagglutinin. Culture supernatants and highly purified MAM exhibited the same haplotype specificity (H-2k-dependent response) for stimulated proliferation of lymphocytes and for induction of interferon in vitro.
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PMID:Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. V. A small basic protein from culture supernatants is a potent T cell mitogen. 348 36

The prototypical superantigen MAM is an extracellular T-cell mitogen produced by Mycoplasma arthritidis, an organism which causes chronic proliferative arthritis of rodents. We here describe purification of MAM to homogeneity. Pure MAM exhibits all of the major properties previously described for partially purified MAM, including preference for H-2E molecules in presention to T cells, V beta T-cell receptor specificity for T-cell activation, and in vivo inhibition of T-cell functions but enhancement of B-cell activity as mediated by the superantigen bridge. Edman degradation of pure MAM gave a 54-residue partial amino-terminal sequence. The oligopeptide MAM15-31-C, synthesized according to the Edman sequence, blocked mitogenicity of MAM and supported assignment of the amino acid sequence.
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PMID:The Mycoplasma arthritidis superantigen MAM: purification and identification of an active peptide. 796 Jan 16

When injected into mice, Mycoplasma arthritidis causes a chronic arthritis that resembles rheumatoid arthritis, histologically. The organism produces a superantigen termed Mycoplasma arthritidis mitogen or MAM, that in humans preferentially expands T cells whose antigen receptors express V beta 17. T cells with this phenotype appear to be increased in rheumatoid synovial effusions. We describe a novel approach to isolating and characterizing human MAM-reactive T-cell lines and determining their T-cell receptor (TCR) V beta usage. Lines were prepared from T cells that clustered with dendritic cells during a 2-day exposure to MAM. Cluster and noncluster fractions of T cells were then expanded by using feeder cells and a polyclonal mitogen. Most of the MAM reactivity was found in dendritic T-cell clusters, as were most of the T cells expressing TCR V beta 17. After expansion, 76% of the cluster-derived T-cell lines were MAM reactive, while no reactivity was seen in cell lines derived from the noncluster fraction. Of the MAM-reactive lines, 49% expressed V beta 17 on some or all of the cells. Cell lines from both cluster and noncluster fractions were analyzed for TCR V beta mRNA expression by PCR amplification. Other V beta genes (5.1, 7, 8, 12, and 20) were found to be expressed by lines that were MAM reactive, although these were not a major component of the cluster-derived T cells. Some non-cluster-derived lines expressed V beta s 17, 12, and 7, but these proved to be nonreactive to MAM. Therefore, dendritic cells can be used to immunoselect and characterize T cells that express superantigen-reactive TCRs.
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PMID:Human T-cell responses to Mycoplasma arthritidis-derived superantigen. 826 19

Mycoplasma arthritidis, an agent of chronic proliferative arthritis of rodents, secretes a potent soluble superantigen, MAM, that is active for both murine and human T and B lymphocytes. We now report the complete nucleotide and amino acid sequence of MAM and show it to be distinct from other proteins and not closely related phylogenetically to other superantigens. Two functional domains on MAM are identified based on the ability of peptides encompassing these regions to inhibit lymphocyte proliferation by the intact MAM molecule. One of these domains shares short sequences or epitopes with other microbial superantigens. The second domain contains the consensus legume lectin motif-beta, which is important for T cell activation by concanavalin (Con) A. MAM and Con A peptides containing this motif are functionally cross reactive, suggesting a novel secondary pathway for T cell activation by MAM.
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PMID:The sequence of the Mycoplasma arthritidis superantigen, MAM: identification of functional domains and comparison with microbial superantigens and plant lectin mitogens. 864 52

Mycoplasma arthritidis, an agent of rodent arthritis, produces a potent superantigen (SAg), MAM. Previous work established that MAM is presented to T cells by murine H-2E or the homologous human HLA-DR molecules and that lymphocytes lacking a functional H-2E molecule fail to respond to MAM. Recently, more potent and purified preparations of MAM of known protein content have become available. This enabled us to more effectively compare the response of MAM with that of other SAgs by using lymphocytes from mice whose cells express different H-2A and HLA-DQ molecules. Here we demonstrate that cells from some H-2E-negative mouse strains respond to higher concentrations of MAM. By use of inbred, congenic, and recombinant mice, we show that these differences are, in fact, exercised at the level of the major histocompatibility complex (MHC) and that allelic polymorphisms at H-2A influence reactivity to MAM. In addition, polymorphisms at HLA-DQ, the human homolog of H-2A, also influence responsiveness to MAM. Cells expressing DQw6 (HLA-DQA1*0103 and DQBI*0601 chains) gave much higher responses to MAM than did cells expressing DQw8 (DQA1*0301 and DQB1*0302 chains). In fact, responses of lymphocytes expressing DQB1*0601 chains homozygously were as high as those observed for cells expressing a functional H-2E molecule. Murine lymphocytes responded less well to staphylococcal enterotoxin B (SEB) and SEA, but mouse cells expressing human MHC molecules gave much higher responses. The patterns of reactivity observed with cells expressing the various murine and human alleles differed for MAM, SEB, and SEA, suggesting that each of these SAgs interacts with different regions or residues on MHC molecules. It has been hypothesized that SAgs might play a role in susceptibility to autoimmune disease. Allelic polymorphisms at MHC loci might therefore influence susceptibility to autoimmune disease by affecting immunoreactivity to specific superantigens.
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PMID:Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. 931 26

Mycoplasma arthritidis causes arthritis in rodents that resembles human rheumatoid arthritis. It produces a superantigen (MAM) that stimulates production of cytokines by making a bridge between lymphocyte T-cell receptor with the appropriate Vbeta chain, and H-2 1-Ealpha MHC class II molecules. Here we studied MAM-induced nitric oxide (NO) production in mouse peritoneal macrophages and found that it was: (1) time and concentration dependent, (2) possibly derived from inducible NOS synthase since it was reduced significantly by amino guanidine pretreatment, (3) restricted to H-2(K) (C3H/HePas and C3H/HeJ) and H-2(d) strains (BALB/c), (4) independent of TLR4 signaling since the coisogenic strains C3H/HePas and C3H/HeJ (TLR4 deficient) produced similar levels of NO following MAM stimulation, (5) potentiated by lipopolysaccharide, and (6) dependent on the presence of nonadherent peritoneal cells. Neutralization of interferon-gamma (IFNgamma in the peritoneal cell cultures with monoclonal antibodies abolished MAM-induced NO production. Addition of rIFNgamma to the adherent cells substituted the nonadherent cells for MAM-induced NO production. A macrophage cell line, J774A.1 (H-2(d)), also produced NO upon MAM stimulation but only when BALB/c spleen lymphocytes were added. Thus, in murine macrophages, MAM induces NO production that is dependent on signaling through MHC class II molecules and IFNgamma but independent of TLR4 expression.
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PMID:Mycoplasma arthritidis superantigen (MAM)-induced macrophage nitric oxide release is MHC class II restricted, interferongamma dependent, and toll-like receptor 4 independent. 1274 62

Mycoplasma arthritidis causes acute polyarthritis in rats and chronic proliferative arthritis in mice. M. arthritidis-induced arthritis serves as a model for arthritis caused by infectious agents and as a model for examining the role of the superantigen MAM (M. arthritidis T-cell mitogen) in the development of autoimmunity. M. arthritidis strain 158-1 is a spontaneous mutant of strain 158 that has a drastic reduction in virulence. We show that the mutant is missing a major antigen of 47 kDa (P47) and has acquired a protein of 67 kDa (P67). P47 and P67 partitioned into the detergent phase by extraction with Triton X-114. Coomassie blue staining of sodium dodecyl sulfate-polyacrylamide gels show that P67 is produced in abundance. Analysis of gel-purified P67 by mass spectrometry led to its identification as a lipoprotein (the open reading frame [ORF] 619 gene product) predicted from the genome sequence of M. arthritidis. PCR analysis of genomic DNA from 158 and 158-1 indicates that P47 and P67 are encoded by the same ORF 619 gene and differ only in the number of repeats in a tandem repeat region. By two-dimensional polyacrylamide gel analysis, no protein differences were detectable between 158 and 158-1 other than P47 and P67. Collectively, the data suggest that the tandem repeat region of P47 and P67 influences disease outcome.
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PMID:Association of a major protein antigen of Mycoplasma arthritidis with virulence. 1561 60


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