Staphylococcal enterotoxins bind H-2Db molecules on macrophages.

Beharka, A.A.; Iandolo, John J.; Chapes, Stephen K.

doi:10.1073/pnas.92.14.6294

Cited by 22 publications

(11 citation statements)

References 34 publications

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“…Immunoprecipitation data suggest an association of LINE-1 product with MHC class I or MHC Class I-like molecules since both 45-and 12-kDa proteins, immunoprecipitated by the Ab d /LINE-1 mAb, were removed from lymphoid cell lysates by preclearing with anti-b2m serum. Such associations with MHC class I molecules have been described for insulin receptor (Chvatchko et al, 1983;Due et al, 1986) and staphylococcal enterotoxin superantigens (Beharka et al, 1995). The MHC fold can perform other functions in addition to presentation of antigenic peptides to T cells.…”

Section: Discussionmentioning

confidence: 82%

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

et al. 2002

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LINE-1 are endogenous mobile genetic elements that have dispersed and accumulated in the genomes of eukaryotes via germline transposition, with up to 100 000 copies in mammalian genomes. LINE-1 elements transpose by reverse transcription of their own transcript. Transposition requires synthesis of a full-length, sense-strand transcripts and proteins encoded by open reading frame (ORF) 1 and ORF2. Although severely repressed in most normal tissues, LINE-1 occasionally leads to disease by insertional mutagenesis. In the present study, Northern blot and in situ hybridization analyses revealed a template-strand transcription of LINE-1 ORF2 (encoding reverse transcriptase, RT) in lymphoid organs and the liver from MRL-+/+ and Fas-deficient MRL/lpr strains and their normal ancestors. While these sense transcripts are restricted to the nucleus in hepatocytes, they are also found in the cytoplasm in splenocytes. In contrast to transcription, ORF2 translation was detected only in MRL strains, as shown by the cytoplasmic labelling of splenic cells obtained with a monoclonal antibody recognizing the LINE-1 RT. This antibody coprecipitated two proteins of 45 and 12 kDa from MRL/lpr lymphoid organ lysates that were removed by pretreatment with anti-b2-microglobulin antiserum, suggesting a structural association between a LINE-1 product and a major histocompatibility complex class I or class I-like molecule.

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Section: Discussionmentioning

confidence: 82%

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

et al. 2002

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“…Immunoinflammatory responses are orchestrated by cytokines, and T-cell mitogens and superantigens are potent stimuli for cytokine production from T cells, monocytes, and macrophages (2,3). In CF there is a misdirected or dysregulated response, since there is a chronic and exuberant immunoinflammatory response without clearance of the pathogen.…”

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confidence: 99%

Pseudomonas aeruginosaExoenzyme S Induces Transcriptional Expression of Proinflammatory Cytokines and Chemokines

Epelman

Bruno

Neely³

et al. 2000

Infect Immun

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Pseudomonas aeruginosa infection of cystic fibrosis patients causes lung damage that is substantially orchestrated by cytokines. In this study, multi-gene probe analysis was used to characterize the ability of the P. aeruginosa mitogen, exoenzyme S, to induce proinflammatory and immunoregulatory cytokines and chemokines. Exoenzyme S strongly induced transcription of proinflammatory cytokines and chemokines (tumor necrosis factor alpha, interleukin-1␣ [IL-1␣], IL-1␤, IL-6, IL-8, MIP-1␣, MIP-1␤, MCP-1, RANTES, and I-309), modest transcription of immunoregulatory cytokines (IL-10 and IL-12p40), and weak transcription of Th1 cytokines (IL-2 and gamma interferon). The response occurred early and subsided without evolving over time. These data suggest that cells responding to exoenzyme S would rapidly express proinflammatory cytokines and chemokines that may contribute to pulmonary inflammation in cystic fibrosis.Virtually all cystic fibrosis (CF) patients are colonized by Pseudomonas aeruginosa, and 90% of those that are colonized die as a result of lung damage (11). One of the hallmarks of the lung damage in CF is an ineffective inflammatory response that results in severe neutrophil-mediated pulmonary damage and an inability to clear the organisms. P. aeruginosa contributes to the lung damage by the production of virulence factors; one of the most important virulence factors, exoenzyme S, has been shown to induce pulmonary damage in animal models (17,29,35), and increased levels of exoenzyme S correlate with human disease (18, 36). The cytotoxicity of exoenzyme S for epithelial cells follows both contact-dependent type III translocation into eukaryotic target cells and contact-independent type III secretion, suggesting two mechanisms of cellular activation: intracellular and extracellular (15,34,35). We have recently described an additional activity: extracellular exoenzyme S is mitogenic for T cells, inducing tremendous T-cell activation (5-7). Exoenzyme-S-induced activation of T cells is neither dependent upon nor inhibited by ADP-ribosyltransferase activity, and this activity is present in exoenzyme S from both purified and recombinant sources (7). Further, we have found that activation by exoenzyme S induces T-cell apoptosis (6). The current studies were performed to determine whether this T-cell activation culminates in the induction of cytokines that have the potential of influencing immunoinflammatory responses or whether apoptosis precludes cytokine transcription.Immunoinflammatory responses are orchestrated by cytokines, and T-cell mitogens and superantigens are potent stimuli for cytokine production from T cells, monocytes, and macrophages (2, 3). In CF there is a misdirected or dysregulated response, since there is a chronic and exuberant immunoinflammatory response without clearance of the pathogen. This response may be a result of altered cytokine induction that includes decreased secretion of the anti-inflammatory cytokine interleukin-10 (IL-10) (13, 28) with concordant increases in proinflammatory cy...

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“…This is a reproducible process that occurs with cells not only of the H-2 b haplotype [15] but also with cells expressing the H-2 k haplotype; the latter being a slightly higher-affinity binding than that seen for H-2D b (10 -5 to 10 -6 M vs. 10 -6 to 10 -7 M). It is curious that others have not readily detected binding to H-2K k or D k .…”

Section: Discussionmentioning

confidence: 90%

“…(2) We demonstrated that superantigens can bind to MHCI molecules other than H-2D b . We had previously shown that SEA had micromolar affinity for MHCII -/-macrophages [14], that antibodies specific for H-2D b could block superantigen binding to macrophages [15] and that H-2D b could directly bind SEA [Wright and Chapes, unpublished results], however, it was not clear if superantigen binding to D b was unique or a phenomenon that occurred with other MHCI molecules. Our data suggest that the MHCI-superantigen interaction may occur more frequently in nature than has been previously acknowledged.…”

Section: Discussionmentioning

confidence: 99%

“…␤-Integrins have been proposed as receptors [11] and despite some failures to implicate MHCI as superantigen receptors [12,13], there is also growing evidence that MHCI can serve as superantigen receptors. Our group [14][15][16] found that MHCII -/-macrophages could be activated by several superantigens and that in vitro biological activity and in vivo pathogenesis could be blocked using MHCI-specific monoclonal antibodies. MHCI knock-out mice also are less susceptible to the pathogenic effects of superantigens [17].…”

Section: Introductionmentioning

confidence: 99%

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Complex high affinity interactions occur between MHCI and superantigens

Chapes

Herpich

1998

Journal of Leukocyte Biology

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Staphylococcal enterotoxins A and C1 (SEA or SEC1) bound to major histocompatibility-I (MHCI) molecules with high affinity (binding constants ranging from 1.1 M to 79 nM). SEA and SEC1 directly bound MHCI molecules that had been captured by monoclonal antibodies specific for H-2K k , H-2D k , or both. In addition, MHCIspecific antibodies inhibited the binding of SEC1 to LM929 cells and SEA competitively inhibited SEC1 binding; indicating that the superantigens bound to MHCI on the cell surface. The affinity and number of superantigen binding sites differed depending on whether MHCI was expressed in the membrane of LM929 cells or whether it was captured. These data support the hypothesis that MHCI molecules can serve as superantigen receptors. J. Leukoc. Biol. 64: 587-594; 1998.

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Staphylococcal enterotoxins bind H-2Db molecules on macrophages.

Cited by 22 publications

References 34 publications

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

Unusual expression of LINE-1 transposable element in the MRL autoimmune lymphoproliferative syndrome-prone strain

Pseudomonas aeruginosaExoenzyme S Induces Transcriptional Expression of Proinflammatory Cytokines and Chemokines

Complex high affinity interactions occur between MHCI and superantigens

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