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Identification and characterization of novel superantigens from Streptococcus pyogenes.

Proft T, Moffatt SL, Berkahn CJ, Fraser JD - J. Exp. Med. (1999)

Bottom Line: All toxins, except rSPE-G, were active on murine T cells, but with reduced potency.The most common targets for the novel SAgs were human Vbeta2.1- and Vbeta4-expressing T cells.This might reflect a specific role for this subset of Vbetas in the immune defense of gram-positive bacteria.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, School of Medicine, University of Auckland, 92019 Auckland, New Zealand.

ABSTRACT
Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma. A fourth novel gene (smez-2) was isolated from the S. pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene. SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin. Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively). SMEZ-2 is the most potent superantigen (SAg) discovered thus far. All toxins, except rSPE-G, were active on murine T cells, but with reduced potency. Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15-65 nM. Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II beta chain. Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G. The most common targets for the novel SAgs were human Vbeta2.1- and Vbeta4-expressing T cells. This might reflect a specific role for this subset of Vbetas in the immune defense of gram-positive bacteria.

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Related in: MedlinePlus

SAg family tree. The family tree was created using the  PileUp program on the GCG package and is based on primary amino acid  sequence homology. The SAg family can be divided into three groups (or  subfamilies) and two individual branches (SPE-H and TSST). SMEZ,  SMEZ-2, SPE-G, and SPE-J build a subfamily together with SPE-C. The  complete DNA sequence of the spe-j gene is not yet available, so only  the 135 COOH-terminal amino acid residues of SPE-J could be used for  the alignment.
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Figure 2: SAg family tree. The family tree was created using the PileUp program on the GCG package and is based on primary amino acid sequence homology. The SAg family can be divided into three groups (or subfamilies) and two individual branches (SPE-H and TSST). SMEZ, SMEZ-2, SPE-G, and SPE-J build a subfamily together with SPE-C. The complete DNA sequence of the spe-j gene is not yet available, so only the 135 COOH-terminal amino acid residues of SPE-J could be used for the alignment.

Mentions: A revised SAg family tree, based on primary amino acid sequence homology (Fig. 2) now shows three general subfamilies: group A comprises SPE-C, SPE-J, SPE-G, SMEZ, and SMEZ-2; group B comprises SEC1-3, SEB, SSA, SPE-A, and SEG; and group C comprises SEA, SEE, SED, SEH, and SEI. Two SAgs, TSST and SPE-H, do not belong to any one of those subfamilies.


Identification and characterization of novel superantigens from Streptococcus pyogenes.

Proft T, Moffatt SL, Berkahn CJ, Fraser JD - J. Exp. Med. (1999)

SAg family tree. The family tree was created using the  PileUp program on the GCG package and is based on primary amino acid  sequence homology. The SAg family can be divided into three groups (or  subfamilies) and two individual branches (SPE-H and TSST). SMEZ,  SMEZ-2, SPE-G, and SPE-J build a subfamily together with SPE-C. The  complete DNA sequence of the spe-j gene is not yet available, so only  the 135 COOH-terminal amino acid residues of SPE-J could be used for  the alignment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887688&req=5

Figure 2: SAg family tree. The family tree was created using the PileUp program on the GCG package and is based on primary amino acid sequence homology. The SAg family can be divided into three groups (or subfamilies) and two individual branches (SPE-H and TSST). SMEZ, SMEZ-2, SPE-G, and SPE-J build a subfamily together with SPE-C. The complete DNA sequence of the spe-j gene is not yet available, so only the 135 COOH-terminal amino acid residues of SPE-J could be used for the alignment.
Mentions: A revised SAg family tree, based on primary amino acid sequence homology (Fig. 2) now shows three general subfamilies: group A comprises SPE-C, SPE-J, SPE-G, SMEZ, and SMEZ-2; group B comprises SEC1-3, SEB, SSA, SPE-A, and SEG; and group C comprises SEA, SEE, SED, SEH, and SEI. Two SAgs, TSST and SPE-H, do not belong to any one of those subfamilies.

Bottom Line: All toxins, except rSPE-G, were active on murine T cells, but with reduced potency.The most common targets for the novel SAgs were human Vbeta2.1- and Vbeta4-expressing T cells.This might reflect a specific role for this subset of Vbetas in the immune defense of gram-positive bacteria.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Medicine, School of Medicine, University of Auckland, 92019 Auckland, New Zealand.

ABSTRACT
Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma. A fourth novel gene (smez-2) was isolated from the S. pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene. SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin. Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively). SMEZ-2 is the most potent superantigen (SAg) discovered thus far. All toxins, except rSPE-G, were active on murine T cells, but with reduced potency. Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15-65 nM. Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II beta chain. Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G. The most common targets for the novel SAgs were human Vbeta2.1- and Vbeta4-expressing T cells. This might reflect a specific role for this subset of Vbetas in the immune defense of gram-positive bacteria.

Show MeSH
Related in: MedlinePlus