Molecular Requirements for MHC Class II α-Chain Engagement and Allelic Discrimination by the Bacterial Superantigen Streptococcal Pyrogenic Exotoxin C

Kasper, Katherine J.; Wang, Xi; Rahman, Ashrafur; Nooh, Mohammed M.; Kotb, Malak; Sundberg, Eric J.; Madrenas, Joaquı́n; McCormick, John K.

doi:10.4049/jimmunol.181.5.3384

Cited by 16 publications

(16 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In STSS, GAS superantigens simultaneously engage T-cell receptor beta-chain variable regions and MHC class II, activating large numbers of T cells in an antigen-independent manner. The result is a massive cytokine response by T cells (lymphotoxin-␣, IL-2, and IFN-␥) and antigen-presenting cells (TNF-␣, IL-1␤, and IL-6), which causes widespread tissue damage, disseminated intravascular thrombosis, and organ dysfunction (7,81,291,292). There is strong epidemiological and genetic evidence that the host MHC class II haplotype influences host susceptibility, with haplotype DR15/DQ6 being less commonly associated with STSS disease and haplotype DR14/DQ5 being more commonly associated with this disease (289,290).…”

Section: Types Of Invasive Infections Caused By Gasmentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

View full text Add to dashboard Cite

SUMMARY Streptococcus pyogenes , also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority.

show abstract

Section: Types Of Invasive Infections Caused By Gasmentioning

confidence: 99%

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Staphylococcal SAgs other than SEB were prepared using a similar approach, and all streptococcal SAgs were generated and purified to apparent homogeneity as previously described. 22,64 Generation of bone marrow-derived DCs Bone marrow cells were flushed with phosphate-buffered saline (PBS) under aseptic conditions from femurs and tibias of B6 or DR4 tg mice and passed through a 70-mm nylon mesh strainer. Erythrocytes were depleted using ACK lysis buffer, and DC precursors were seeded at 1Â10 6 cells ml À1 in a six-well polystyrene plate and cultured for 6 days in complete medium containing 10 ng ml À1 each of murine granulocyte-monocyte colony stimulating factor and IL-4 (PeproTech Inc., Rocky Hill, NJ, USA).…”

Section: Bacterial Sagsmentioning

confidence: 99%

CD1d‐independent activation of mouse and human iNKT cells by bacterial superantigens

et al. 2011

View full text Add to dashboard Cite

Invariant NKT (iNKT) cells are infrequent but important immunomodulatory lymphocytes that exhibit CD1d-restricted reactivity with glycolipid Ags. iNKT cells express a unique T-cell receptor (TCR) composed of an invariant a-chain, paired with a limited range of b-chains. Superantigens (SAgs) are microbial toxins defined by their ability to activate conventional T cells in a TCR b-chain variable domain (Vb)-specific manner. However, whether iNKT cells are directly activated by bacterial SAgs remains an open question. Herein, we explored the responsiveness of mouse and human iNKT cells to a panel of staphylococcal and streptococcal SAgs and examined the contribution of major histocompatibility complex (MHC) class II and CD1d to these responses. Bacterial SAgs that target mouse Vb8, such as staphylococcal enterotoxin B (SEB), were able to activate mouse hybridoma and primary hepatic iNKT cells in the presence of mouse APCs expressing human leukocyte antigen (HLA)-DR4. iNKT cell-mediated cytokine secretion in SEB-challenged HLA-DR4-transgenic mice was CD1d-independent and accompanied by a high interferon-c:interleukin-4 ratio consistent with an in vivo Th1 bias. Furthermore, iNKT cells from SEB-injected HLA-DR4-transgenic mice, and iNKT cells from SEB-treated human PBMCs, showed early activation by intracellular cytokine staining and CD69 expression. Unlike iNKT cell stimulation by a-galactosylceramide, stimulation by SEB did not induce TCR downregulation of either mouse or human iNKT cells. We conclude that Vb8-targeting bacterial SAgs can activate iNKT cells by utilizing a novel pathway that requires MHC class II interactions, but not CD1d. Therefore, iNKT cells fulfill important effector functions in response to bacterial SAgs and may provide attractive targets in the management of SAg-induced illnesses.

show abstract

“…The current model for superantigen activity suggests that native, unprocessed SAg bind directly to the -helical chain of the MHC class II, outside the peptide binding groove of the antigen presenting cell (APC) [5]. This binding takes place without proteolytic degradation and fragmentation, internalization, and re-expression of the SAg degraded short fragments on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Rasooly¹,

Paula²,

Hernlem³

2011

OJI

View full text Add to dashboard Cite

show abstract

Molecular Requirements for MHC Class II α-Chain Engagement and Allelic Discrimination by the Bacterial Superantigen Streptococcal Pyrogenic Exotoxin C

Cited by 16 publications

References 63 publications

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

CD1d‐independent activation of mouse and human iNKT cells by bacterial superantigens

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

Contact Info

Product

Resources

About

Molecular Requirements for MHC Class II α-Chain Engagement and Allelic Discrimination by the Bacterial Superantigen Streptococcal Pyrogenic Exotoxin C

Cited by 16 publications

References 63 publications

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

CD1d‐independent activation of mouse and human iNKT cells by bacterial superantigens

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4&lt;sup&gt;+&lt;/sup&gt; T cells

Contact Info

Product

Resources

About

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells