Article abstract
Nature Immunology 9, 282 - 291 (2008)
Published online: 20 January 2008 | doi:10.1038/ni1559
T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation
Sarah E Henrickson1, Thorsten R Mempel1, Irina B Mazo1, Bai Liu2, Maxim N Artyomov3, Huan Zheng4, Antonio Peixoto1, Michael P Flynn1, Balimkiz Senman1, Tobias Junt1, Hing C Wong2, Arup K Chakraborty3,4,5 & Ulrich H von Andrian1
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.
- Department of Pathology and the Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
- Altor BioScience, Miramar, Florida 33025, USA.
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
- Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Correspondence to: Ulrich H von Andrian1 e-mail: uva@cbr.med.harvard.edu
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