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Titolo:
Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock
Autore:
Arad, G; Hillman, D; Levy, R; Kaempfer, R;
Indirizzi:
Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 -91120 Jerusalem, Israel
Titolo Testata:
JOURNAL OF LEUKOCYTE BIOLOGY
fascicolo: 6, volume: 69, anno: 2001,
pagine: 921 - 927
SICI:
0741-5400(200106)69:6<921:SABTCG>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
STAPHYLOCOCCAL-ENTEROTOXIN-B; TUMOR-NECROSIS-FACTOR; COMPLEX CLASS-II; AUREUS TOXIN SUPERANTIGENS; RECEPTOR-BETA-CHAIN; HUMAN T-CELLS; CRYSTAL-STRUCTURE; BINDING-SITES; HUMAN INTERLEUKIN-2; EXPRESSION;
Keywords:
toxic shock; T-cell activation; antagonist peptide; protective immunity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Kaempfer, R Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Virol, IL-91120 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91120 alem, Israel
Citazione:
G. Arad et al., "Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock", J LEUK BIOL, 69(6), 2001, pp. 921-927

Abstract

Bacterial superantigens trigger an excessive, Th1-cytokine response leading to toxic shock. We designed a peptide antagonist that inhibits SEB-induced expression of human genes for IL-2, IFN-gamma, and TNF-beta, cytokines that mediate shock, The peptide antagonist shows homology to a beta -strand-hinge-alpha -helix domain that is conserved structurally in superantigens produced by Staphylococcus aureus and Streptococcus pyogenes yet remote from known binding sites for the major histocompatibility class II molecule and T-cell receptor, For Th1-cell activation, superantigens depend on this domain. The peptide protected mice against lethal challenge with SEE or SEA. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed broad-spectrum, protective immunity, which rendered them resistant tofurther lethal challenges with different staphylococcal and streptococcal superantigens. Thus, the lethal effect of superantigens, mediated by Th1 cytokines, can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells takes place.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 07:14:36