Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength

被引:408
作者
Egen, JG [1 ]
Allison, JP [1 ]
机构
[1] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Canc Res Lab, Berkeley, CA 94720 USA
关键词
D O I
10.1016/S1074-7613(01)00259-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD28 and CTLA-4 engagement with B7 expressed by APCs generates critical regulatory signals for T cell activation. CD28 is expressed on the T cell surface and enhances T cell expansion, while CTLA-4 localizes primarily to an intracellular compartment and inhibits T cell proliferation. We demonstrate that CTLA-4 has several unique trafficking properties that may regulate its ability to attenuate a T cell response. Importantly, accumulation of CTLA-4 at the immunological synapse is proportional to the strength of the TCR signal, suggesting that cells receiving stronger stimuli are more susceptible to CTLA-4-mediated inhibition. This may represent a novel feedback control mechanism in which a stimulatory signal regulates the recruitment of an inhibitory receptor to a functionally relevant site on the cell surface.
引用
收藏
页码:23 / 35
页数:13
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