CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines

被引:195
作者
Wang, YF
Kelly, CG
Karttunen, JT
Whittall, T
Lehner, PJ
Duncan, L
MacAry, P
Younson, JS
Singh, M
Oehlmann, W
Cheng, GH
Bergmeier, L
Lehner, T [1 ]
机构
[1] KCL, Guys Kings & St Thomas Med Sch, Dept Oral Med, Peter Gorer Dept Immunobiol, London, England
[2] KCL, Guys Kings & St Thomas Med Sch, Dept Oral Med, Immunol Unit, London, England
[3] Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Dept Pathol,Div Immunol, Cambridge CB2 2QQ, England
[4] Lionex Diagnost & Therapeut GmbH, Braunschweig, Germany
[5] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA
基金
英国惠康基金;
关键词
D O I
10.1016/S1074-7613(01)00242-4
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The 70 kDa mycobacterial heat shock protein (Mtb HSP70) stimulates mononuclear cells to release CC-chemokines. We now show that this function of Mtb HSP70, but not human HSP70, is dependent on the cell surface expression of CD40. Deletion of the CD40 cytoplasmic tail abolished, and CD40 antibody inhibited, Mtb HSP70 stimulation of CC-chemokine release. Mtb HSP70 stimulated THP1, KG1 cells, and monocyte-derived dendritic cells to produce RANTES. Specific binding of CD40-transfected HEK 293 cells to Mtb HSP70 was demonstrated by surface plasmon resonance. Coimmunoprecipitation of Mtb HSP70 with CD40 indicates a physical association between these molecules. The results suggest that CD40 is critical in microbial HSP70 binding and stimulation of RANTES production.
引用
收藏
页码:971 / 983
页数:13
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