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

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

Research output: Contribution to journalArticlepeer-review

314 Scopus citations

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.

Original languageEnglish
Pages (from-to)282-291
Number of pages10
JournalNature immunology
Volume9
Issue number3
DOIs
StatePublished - Mar 2008

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