T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation

T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation
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DOI:
10.1038/ni1559
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发表时间:
2008-03-01
期刊:
影响因子:
30.5
通讯作者:
von Andrian, Ulrich H.
von Andrian, Ulrich H.
中科院分区:
医学1区
文献类型:
--
作者:
Henrickson, Sarah E.;Mempel, Thorsten R.;von Andrian, Ulrich H.

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在归巢到淋巴结后,CD8(+) T细胞被树突状细胞(dc)启动,分为三个阶段。在第一阶段,T细胞与dc进行几个小时的短暂连续接触,而第二阶段的特点是稳定的T - dc相互作用。我们在这里表明,第一阶段的持续时间和T细胞活化动力学与每个DC的同源肽复合物和主要组织相容性复合物(pMHC)的数量以及每个淋巴结抗原呈递DC的密度呈负相关。很少的pMHC复合物是诱导成熟的T细胞活化和效应分化所必需的。然而,在低于阈值抗原剂量(部分由pMHC稳定性决定)的情况下,T细胞活化和过渡到第二阶段都不会发生。因此,第一阶段允许T细胞对抗原剂量进行综合“测量”,以确定后续T细胞参与免疫反应。
After homing to lymph nodes, CD8(+) T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinetics correlated inversely with the number of complexes of cognate peptide and major histocompatibility complex (pMHC) per DC and with the density of antigen-presenting DCs per lymph node. Very few pMHC complexes were necessary for the induction of full-fledged T cell activation and effector differentiation. However, neither T cell activation nor transition to phase two occurred below a threshold antigen dose determined in part by pMHC stability. Thus, phase one permits T cells to make integrated 'measurements' of antigen dose that determine subsequent T cell participation in immune responses.