KAEMPFER R, ARAD G, LEVY R, HILLMAN D; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 530.

Hebrew Univ.-Hadassah Med. Sch., Jerusalem, Israel

Bacterial superantigens are among the most lethal of toxins. By activating up to 50% of T cells, they trigger an excessive cellular immune response leading to toxic shock. The high cytokine levels produced in response to superantigens have obstructed efforts to block downstream phenomena in the toxicity cascade set off by a pyrogenic toxin, for example, with mAbs. We designed a peptide antagonist that inhibits superantigen-induced expression of human genes for IL-2, IFN-gamma and TNF-beta, Th1 cytokines that mediate shock. The peptide shows homology to a beta-strand-hinge-alpha-helix domain that is structurally conserved 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. Superantigens depend for T-cell activation on this domain. The peptideprotected mice against lethal challenge with staphylococcal and streptococcal superantigens. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed protective antibodies to superantigen that render them resistant to further lethal challenges, even with different superantigens. Thus, the lethal effect of superantigens 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. Reference: Arad, G., Levy, R. Hillman, D. and Kaempfer, R. (2000). Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation. Nature Medicine 6, 414-421.KEYWORDS: Antagonist; Superantigen; Toxic shock

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Antibodies
• Cytokines
• Humans
• Interleukin-2
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Peptides
• Shock, Septic
• Staphylococcus
• Staphylococcus aureus
• Streptococcus
• Streptococcus pyogenes
• Superantigens
• T-Lymphocytes
• immunology

Other ID:

• GWAIDS0011435

UI: 102248933

From Meeting Abstracts