ENGAGEMENT OF MHC CLASS-II MOLECULES BY STAPHYLOCOCCAL SUPERANTIGENS ACTIVATES SRC-TYPE PROTEIN-TYROSINE KINASES

被引:58
作者
MORIO, T
GEHA, RS
CHATILA, TA
机构
[1] HARVARD UNIV, CHILDRENS HOSP, SCH MED, DIV IMMUNOL, BOSTON, MA 02115 USA
[2] HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA
关键词
MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II MOLECULES; SUPERANTIGENS; FGR; LYN; HCK;
D O I
10.1002/eji.1830240325
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Staphylococcal exotoxins (SE) are superantigens that bind to monomorphic determinants on major histocompatibility complex (MHC) class II molecules and stimulate human peripheral blood T lymphocytes in a V beta-specific manner. SE also deliver activation signals via MHC class II molecules that initiate cell adhesion and cytokine gene transcription. These events are preceded by tyrosine phosphorylation and are antagonized by inhibitors of tyrosine kinases, indicating an essential role for these kinases in signaling via class II molecules. We report that stimulation of human peripheral blood monocytes with SE induced rapid and selective activation of the src-related protein tyrosine kinases (PTK) fgr and hck. SE also induced the activation of fgr and lyn in B cells. PTK activation by SE required MHC class II expression, and was greatly potentiated in the presence of T cells bearing toxin-specific V beta chains. These results indicate that in addition to their antigen and superantigen-presenting function, MHC class II molecules act as signal-transducing receptors that are coupled to src-type PTK.
引用
收藏
页码:651 / 658
页数:8
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