T cell antigen recognition at the cell membrane.

T cell antigen recognition at the cell membrane.
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DOI:
10.1016/j.molimm.2012.05.004
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发表时间:
2012-10
影响因子:
3.6
通讯作者:
Zhu C
Zhu C
中科院分区:
医学3区
文献类型:
--
作者:
Huang J;Meyer C;Zhu C

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T细胞表面上的T细胞抗原受体(TCR)特异性结合抗原呈递细胞(APC)表面上呈递的特定肽结合的主要组织相容性复合物(pMHC)。这种相互作用是T细胞抗原识别和活化中的关键事件。大多数研究已经使用表面等离子体共振(SPR)来使用纯化的蛋白质测量溶液中TCR-pMHC相互作用的体外结合动力学。然而,这些测量在生理学上并不精确,因为TCR和pMHC都是由其细胞环境调节的膜相关分子。最近,单分子Förster共振能量转移(FRET)和单分子力学测定被用于测量活T细胞表面上TCR-pMHC相互作用的原位结合动力学。这些研究为T细胞抗原识别的生化基础提供了令人兴奋的见解,并表明TCR以非常快的动力学连续地与少量抗原接合,以最大化TCR信号传导和灵敏度。
T cell antigen receptors (TCR) on the surface of T cells bind specifically to particular peptide bound major histocompatibility complexes (pMHC) presented on the surface of antigen presenting cells (APC). This interaction is a key event in T cell antigen recognition and activation. Most studies have used surface plasmon resonance (SPR) to measure the in vitro binding kinetics of TCR-pMHC interactions in solution using purified proteins. However, these measurements are not physiologically precise, as both TCRs and pMHCs are membrane-associated molecules which are regulated by their cellular environments. Recently, single-molecule förster resonance energy transfer (FRET) and single-molecule mechanical assays were used to measure the in situ binding kinetics of TCR-pMHC interactions on the surface of live T cells. These studies have provided exciting insights into the biochemical basis of T cell antigen recognition and suggest that TCRs serially engage with a small number of antigens with very fast kinetics in order to maximize TCR signaling and sensitivity.
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