Bacterial superantigens induce Vβ-specific T cell receptor internalization
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- 作者：Makida ; Ryuji ; Hofer ; Michael F. ; Takase ; Kozo ; Cambier ; John C. ; Leung ; Donald Y. M.
- 关键词：superantigens ; T cell receptor ; Staphylococcus ; toxins
- 刊名：Molecular Immunology
- 出版年：1996
- 出版时间：July, 1996
- 年：1996
- 卷：33
- 期：10
- 页码：891-900
- 全文大小：880 K
文摘
Staphylococcal enterotoxins can cause toxic shock syndrome and autoimmune diseases. Circulating T cells from these diseases have a very wide range of expression in particular T cell receptor (TCR) β chain variable regions (Vβ). One possibility for this wide range of TCR Vβ expression is that during acute infection with organisms secreting superantigens (SAg) these potent molecules might modulate TCR expression. To test this hypothesis, we investigated the potential effects of SAg on TCR Vβ cell surface expression. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with staphylococcal SAg. Toxic shock syndrome toxin-1 (TSST-1) induced downregulation of Vβ2 expression, whereas staphylococcal enterotoxin (SE) B induced Vβ3-and Vβ12-specific downregulation. TSST-1 did not interfere with anti-Vβ2 mAb binding. Therefore, this downregulation was not due to steric hindrance of Ab binding by TSST-1. TSST-1 induced Vβ2 downregulation was time-, dose- and temperature-dependent. CD3 expression decreased in parallel with reduction of Vβ expression. CD4 and CD8 expression were only slightly decreased. CD2, CD25 and HLA-DR expression were upregulated following TSST-1 stimulation of T cell lines. To investigate the fate of TCR after toxin stimulation, Vβ8+ Jurkat T cells were incubated with SEE which is known to stimulate Vβ8+ T cells, and analysed with fluoresence microscopy, and immunoprecipitation and Western blotting. After SEE stimulation, there was an increase in Vβ8 molecules found in the cytoplasm which correlated with loss of cell surface Vβ8 molecules, suggesting internalization of cell surface Vβ8 molecules was induced by SEE stimulation. Shedding of Vβ8 molecules into the culture supernatant was not detected. These data demonstrate that SAg mediated downregulation of TCR expression occurs primarily as the result of TCR internalization. This downregulation phenomenon may have physiological and pathological consequences in patients infected with Staphylococcus aureus.