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 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bacterial toxic mitogens or superantigens are a family of related proteins that elicit potent T cell proliferative responses. These responses require APC that express MHC class II proteins, but they are not MHC restricted and they do not depend on a processing step, presumably because these mitogens bind directly to MHC class II molecules. These mitogens stimulate T cells by interacting in an unknown way with the portion of the TCR encoded by certain V beta gene segments. In this paper, we explore the importance of MHC class II polymorphism in T cell responses to staphylococcal enterotoxins. We find that certain MHC molecules present SEB to V beta 8-bearing T cells far better than others. These data suggest that one route of host defence against bacterial toxic mitogens may be to alter MHC class II molecules so that stimulation is inhibited.
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PMID:Control of T cell responses to staphylococcal enterotoxins by stimulator cell MHC class II polymorphism. 190 96

We have examined the responses of cloned T cell lines and of normal T cells to staphylococcal enterotoxins A, B, and C1 (SEA, SEB, and SEC1). SEA, SEB, and SEC1 are all very potent mitogens for T cells in the presence of Ia+ APC. The minimal activating dose of all these SE varies from 1 to 100 ng/ml. As determined by mAb blocking of the responses of both normal T cells and cloned T cell lines, SEA required either the I-A or the I-E molecule on APC for stimulating T cells, whereas SEB required the I-E molecule predominantly over I-A molecule. The TCR:CD4 complex is also involved in the response to SE. The responses to SEB and SEC1 were inhibited by anti-V beta 8 antibody F23.1, whereas the response to SEA and to PHA was not affected by this antibody. Anti-CD4 effectively inhibited responses to all SE but not to PHA. The involvement of the TCR was also confirmed by flow microfluorimetry analysis of T cell blasts responding to SE and the responses of a panel of cloned T cell lines, both of which showed that V beta 8+ T cells preferentially responded to SEB, whereas V beta 8+ T cells failed to respond to SEA. By using fixed APC, it could be shown that processing is not required for the presentation of SE. Furthermore, pulsing experiments showed that SEB can bind to relevant sites on either B cells or T cells, whereas with conventional Ag only prepulsing of the APC has worked. In one case, SEB activates a cloned T cell line in the absence of APC, and this same clone also responds directly to anti-V beta 8 antibody. Thus, SEB appears to bring together V beta 8-expressing TCR with the I-E molecule, whereas SEA apparently has the same effect on TCR expressing different V beta with either the I-A or the I-E molecule, probably depending upon which TCR is bound. The close resemblance between T cell responses to SE and those to mixed-lymphocyte stimulating (Mls) locus suggests to us that a novel SE-like protein that binds both to class II MHC molecules on the APC surface and to V beta gene products on TCR could be the product of the Mls locus.
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PMID:Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC. 213 3

Responses to the superantigen Mls are characterized by proliferation of a significant percentage of T cells expressing receptors encoded by one or a few V beta gene segments. Apparently similar responses are elicited by the staphylococcal enterotoxins (SEs) and other bacterial superantigens. We have observed that T cells can be stimulated by the bacterial superantigen SEs presented by either spleen cells or fibroblasts transfected with the appropriate MHC class II genes. However, the results in this study showed that T cells required more than 100-fold higher concentrations of SEA in the presence of L cell transfectants than spleen APC, although T cell responses to SEB and several other toxins presented by the two types of APC were equivalent. Thus, L cell transfectants have a selective defect in presenting SEA. These data suggest that fibroblasts lack a component required by SEA to stimulate certain T cells, and lead us to propose an alternative model for bacterial superantigen mitogenesis in which the superantigen binds to and modifies the behavior of an endogenous co-ligand.
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PMID:Stimulator cell type influences the response of T cells to staphylococcal enterotoxins. 790 98

Different isoforms of soluble staphylococcal enterotoxins (SE): SEB, SEC-1 and SEC-2, were shown to stimulate bovine T cell proliferation, expression of cytokine messages, and IgG production. Intact metabolic function of APC was not required since peripheral blood mononuclear cells (PBMC), UV-irradiated prior to or following incubation with SE, were both capable of presenting SE, while PBMC treated with MAbs against MHC II lost the ability to stimulate T cell proliferation. SE caused approximately two fold increase of CD4+, and CD8+ T cells, but not MHC II+ APC or B cells. This model system suggests that SE transduces not only T cell activation signal, but also a non-proliferative signal for primary B cells to produce polyclonal IgG. We hypothesize that enterotoxin virulence may be in part due to its effect on activating the immune system.
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PMID:Staphylococcal enterotoxin is a bovine T cell superantigen. 854 44

The aim of this study was to investigate the mechanisms by which B7-related costimulatory molecules (CD80, CD86) increase T-cell responsiveness to extracellular ligands. As a model study, the in vitro response of purified splenic CD4+ T cells to a bacterial superantigen, SEB, was characterized. Previous analysis of this experimental model led us to conclude that expression of B7-related molecules is strictly required in order to activate CD4+ T cells in the presence of bacterial superantigens. In the present report, we demonstrate that antigen-presenting cell-derived costimulatory signals regulate the kinetics of interleukin-2 (IL-2) production by SEB-activated splenic CD4+ T cells. Indeed, experiments performed with purified subpopulations of antigen-presenting cells and using B7-transfected cell lines indicated that increased levels of CD80 and/or CD86 cell surface expression is associated with a faster kinetics of IL-2 production in response to SEB. Accordingly, blocking of CD80 or CD86-derived signals by specific monoclonal antibodies led to a slower kinetics of IL-2 production in response to SEB. Thus these data demonstrate that similar strength of signal through the T-cell receptor can lead to immune responses displaying distinct kinetics depending on the level of costimulatory ligands on APC.
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PMID:Costimulation regulates the kinetics of interleukin-2 response to bacterial superantigens. 894 21

Several models have been suggested above, describing possible modes of spindle checkpoint action: 1. Cdc20 sequestration (by Mad2-Cdc20 and/or MCC). 2. Stable MCC-APC/C association. 3. Cdc20 turnover (in budding yeast). 4. Cdc20-APC/C modification (by Mps1, Bub1, MAPK, Aurora B or BubR1 kinases). Several of these mechanisms could affect APC/C activity by modifying, competing for, and/or blocking the binding site(s) for its substrates. Alternatively, they could reduce the processivity of ubiquitination of substrates, or prevent the release of substrates and thereby reduce substrate turnover. Indeed, the processivity of ubiquitination can determine the order of destruction of APC/C substrates (Rape et al., 2006). Most substrates require multiple APC/C binding events in order to build polyubiquitin chains, and only polyubiquitinated substrates are recognised by the 26S proteasome for destruction. Thus, if the processivity of ubiquitination or the turnover of APC/C substrates were impaired in mitosis, the degradation of securin and cyclin would no longer take place, which would result in mitotic arrest. Our results have highlighted the importance of Mad3 as an anaphase inhibitor, and suggest that it usually acts in concert with Mad2 to efficiently inhibit Cdc20-APC/C. Further experiments are necessary to fully understand their mechanism of action, and this will require a wide range of approaches including dynamic studies of the 'flux' of Mad2 and BubR1 through signalling scaffolds, further structural insights, the identification of important phosphorylation sites on both the checkpoint proteins and Cdc20-APC/C, and an in vitro reconstitution of MCC inhibition of the APC/C. We look forward to seeing the complex regulation of mitotic progression being described over the coming years.
SEB Exp Biol Ser 2008
PMID:The spindle checkpoint: how do cells delay anaphase onset? 1836 27