A TOXIC SHOCK SYNDROME TOXIN-1 MUTANT THAT DEFINES FUNCTIONAL SITE CRITICAL FOR T-CELL ACTIVATION

被引:25
作者
CULLEN, CM [1 ]
BLANCO, LR [1 ]
BONVENTRE, PF [1 ]
CHOI, E [1 ]
机构
[1] UNIV CINCINNATI, COLL MED, DEPT MOLEC GENET BIOCHEM & MICROBIOL, CINCINNATI, OH 45267 USA
关键词
D O I
10.1128/IAI.63.6.2141-2146.1995
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toxic shock syndrome toxin 1 (TSST-1), a superantigen produced by Staphylococcus aureus, is a causative agent of toxic shock syndrome (TSS). This superantigen is a potent stimulator of T cells and macrophages/monocytes, resulting in the release of cytokines that are implicated in the pathogenesis of TSS. This study characterizes a mutant TSST-1, derived by site-directed mutagenesis, that has an alanine substitution at histidine 135 (mutant 135). This single-amino-acid change results in a mutant toxin that has lost mitogenic activity for T cells. In contrast to wild-type TSST-1, this mutant does not induce T cells to express interleukin-2, gamma interferon, or tumor necrosis factor beta (TNF-beta). The inability of mutant 135 to activate T cells is not due to a lack of binding to the class II major histocompatibility complex receptor. In addition, the mutant TSST-1 does not induce expression of TNF-alpha, which plays a role in the development of lethal shock. The lack of TNF-alpha induction by mutant 135 is likely due to its inability to activate T cells. These data suggest that the mutation at histidine 135 in TSST-1 affects toxin interactions with the T-cell receptor rather than the class II major histocompatibility complex receptor.
引用
收藏
页码:2141 / 2146
页数:6
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