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


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.

SUBMITTER: Henrickson SE 

PROVIDER: S-EPMC2698867 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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

Henrickson Sarah E SE   Mempel Thorsten R TR   Mazo Irina B IB   Liu Bai B   Artyomov Maxim N MN   Zheng Huan H   Peixoto Antonio A   Flynn Michael P MP   Senman Balimkiz B   Junt Tobias T   Wong Hing C HC   Chakraborty Arup K AK   von Andrian Ulrich H UH  

Nature immunology 20080120 3


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  ...[more]

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