Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins

Beharka, A.A.; Armstrong, Jason W.; Iandolo, John J.; Chapes, Stephen K.

doi:10.1128/iai.62.9.3907-3915.1994

Cited by 22 publications

(7 citation statements)

References 39 publications

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“…Low-affinity interactions have been seen between other superantigens and components of eukaryotic cell surfaces. Beharka et al found lowaffinity binding of SEA and SEB to macrophages from transgenic mice with knockout mutations in the class II genes (5). The low-affinity binding of SEA was proposed to be either to one of several distinct membrane proteins or to class I MHC.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the superantigenic activity of mutant and allelic forms of streptococcal pyrogenic exotoxin A

Kline

Collins

1996

Infect Immun

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Infections with Streptococcus pyogenes (group A streptococcus) can result in the recently described streptococcal toxic shock syndrome (STSS), which is characterized by rashes, hypotension, multiorgan failure, and a high mortality rate. S. pyogenes isolates associated with STSS usually produce streptococcal pyrogenic exotoxin A (SpeA), a bacterial superantigen capable of stimulating host immune cells. Most of the symptoms of STSS are believed to result from cytokine release by the stimulated cells. To better understand the pathogenesis of STSS, we began studies on the SpeA-immune cell interaction. We generated 20 mutant forms of SpeA1 (SpeA encoded by allele 1), and the mutant toxins were analyzed for mitogenic stimulation of human peripheral blood mononuclear cells, affinity for class II major histocompatibility complex molecules (DQ), and disulfide bond formation. Residues necessary for each of these functions were identified. There are four alleles of speA, and STSS strains usually contain either allele 2 or allele 3. The product of allele 2, SpeA2, had slightly higher affinity for the class II MHC molecule compared with SpeA1 but not significantly greater mitogenic activity. SpeA3, however, was significantly increased in mitogenic activity and affinity for class II MHC compared with SpeA1. Thus, we have evidence that the toxin encoded by some of the highly virulent S. pyogenes STSSassociated isolates is a more active form of SpeA.

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Section: Discussionmentioning

confidence: 99%

Analysis of the superantigenic activity of mutant and allelic forms of streptococcal pyrogenic exotoxin A

Kline

Collins

1996

Infect Immun

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“…They also mentioned that another group of researchers (107) could not precipitate MHC class II molecules with commercial ETA, possibly because the toxin did not bind to the molecule. Similarly, ETA and ETB purified from S. aureus strains could stimulate spleen cells of transgenic mutant mice deficient in the expression of MHC class II antigens (45), as well as MHC class II deficient macrophages, but did not bind to class II molecules (28). Further arguments against superantigenic activity presented by Cavarelli et al (44) are as follows: (i) the characteristic symptoms of cytokines (including rash, fever, and hypotension) induced by the action on lymphocytes of other superantigens such as TSST-1 and the enterotoxins is not seen with the ETs; (ii) histological examination of skin from patients with SSSS does not show any recruitment of immune system cells; and (iii) none of the other known superantigens possess the speculated hydrolytic activity of the ETs.…”

Section: Superantigenic Activitymentioning

confidence: 99%

Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins Causing Staphylococcal Scalded-Skin Syndrome

et al. 1999

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SUMMARY The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin disorder that predominantly affects children. Clinical features of SSSS vary along a spectrum, ranging from a few localized blisters to generalized exfoliation covering almost the entire body. The toxins act specifically at the zona granulosa of the epidermis to produce the characteristic exfoliation, although the mechanism by which this is achieved is still poorly understood. Despite the availability of antibiotics, SSSS carries a significant mortality rate, particularly among neonates with secondary complications of epidermal loss and among adults with underlying diseases. The aim of this article is to provide a comprehensive review of the literature spanning more than a century and to cover all aspects of the disease. The epidemiology, clinical features, potential complications, risk factors, susceptibility, diagnosis, differential diagnoses, investigations currently available, treatment options, and preventive measures are all discussed in detail. Recent crystallographic data on the toxins has provided us with a clearer and more defined approach to studying the disease. Understanding their mode of action has important implications in future treatment and prevention of SSSS and other diseases, and knowledge of their specific site of action may provide a useful tool for physiologists, dermatologists, and pharmacologists.

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“…1) also serve as superantigen receptors (71,72,174,224). Recent studies have suggested that other surface molecules including integrins may also be involved in binding superantigens (11,32). The binding of superantigens to the TCR and/or to class II molecules triggers intracellular biochemical signals that program a number of events leading to cell activation, differentiation, proliferation, and the release of inflammatory cytokines (36,177).…”

Section: Superantigens: Definition and Mechanism Of Immune Stimulationmentioning

confidence: 99%

Bacterial pyrogenic exotoxins as superantigens

1995

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The recent discovery of the mode of interaction between a group of microbial proteins known as superantigens and the immune system has opened a wide area of investigation into the possible role of these molecules in human diseases. Superantigens produced by certain viruses and bacteria, including Mycoplasma species, are either secreted or membrane-bound proteins. A unique feature of these proteins is that they can interact simultaneously with distinct receptors on different types of cells, resulting in enhanced cell-cell interaction and triggering a series of biochemical reactions that can lead to excessive cell proliferation and the release of inflammatory cytokines. However, although superantigens share many features, they can have very different biological effects that are potentiated by host genetic and environmental factors. This review focuses on a group of secreted pyrogenic toxins that belong to the superantigen family and highlights some of their structural-functional features and their roles in diseases such as toxic shock and autoimmunity. Deciphering the biological activities of the various superantigens and understanding their role in the pathogenesis of microbial infections and their sequelae will enable us to devise means by which we can intervene with their activity and/or manipulate them to our advantage.

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Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins

Cited by 22 publications

References 39 publications

Analysis of the superantigenic activity of mutant and allelic forms of streptococcal pyrogenic exotoxin A

Analysis of the superantigenic activity of mutant and allelic forms of streptococcal pyrogenic exotoxin A

Clinical, Microbial, and Biochemical Aspects of the Exfoliative Toxins Causing Staphylococcal Scalded-Skin Syndrome

Bacterial pyrogenic exotoxins as superantigens

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