Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen

Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen
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DOI:
10.1016/s1074-7613(01)00096-6
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发表时间:
2001-02-01
期刊:
影响因子:
32.4
通讯作者:
Schneck, JP
Schneck, JP
中科院分区:
医学1区
文献类型:
--
作者:
Fahmy, TM;Bieler, JG;Schneck, JP

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虽然已知活化的T细胞对抗原刺激具有增强的生物应答,但这种增加的敏感性的生物物理基础仍然未知。在这里,我们表明,在活化的T细胞上,TCR对肽-MHC复合物的亲合力比初始T细胞的TCR亲合力高20至50倍。这种对肽-MHC的增加的亲合力依赖于TCR重组,并且对T细胞膜的胆固醇含量敏感。结合数据的分析表明,增强的亲合力是由于活化的T细胞上TCR的交联增加。TCR亲合力的活化诱导的膜(AIM)变化代表了先前未被认识到的增加活化T细胞对外周中少量抗原的敏感性的手段。
While activated T cells are known to have enhanced biological responses to antigen stimulation, the biophysical basis of this increased sensitivity remains unknown. Here, we show that, on activated T cells, the TCR avidity for peptide-MHC complexes is 20- to 50-fold higher than the TCR avidity of naive T cells. This increased avidity for peptide-MHC depends on TCR reorganization and is sensitive to the cholesterol content of the T cell membrane. Analysis of the binding data indicates the enhanced avidity is due to increases in cross-linking of TCR on activated T cells. Activation-induced membrane (AIM) changes in TCR avidity represent a previously unrecognized means of increasing the sensitivity of activated T cells to small amounts of antigen in the periphery.