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

细胞对抗原剂量的感知控制着与树突状细胞的相互作用行为,并设定了 T 细胞活化的阈值

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作者:Sarah E Henrickson, Thorsten R Mempel, Irina B Mazo, Bai Liu, Maxim N Artyomov, Huan Zheng, Antonio Peixoto, Michael P Flynn, Balimkiz Senman, Tobias Junt, Hing C Wong, Arup K Chakraborty, Ulrich H von Andrian

Abstract

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.

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