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

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. 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 journal › Article › peer-review

340 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 language	English
Pages (from-to)	282-291
Number of pages	10
Journal	Nature Immunology
Volume	9
Issue number	3
DOIs	https://doi.org/10.1038/ni1559
State	Published - Mar 2008
Externally published	Yes

Bibliographical note

Funding Information:
We thank T. Buschman for assistance with programming; M. van den Broek for providing cDNA constructs for the P14 TCR; and G. Cheng and J. Alton for technical and secretarial assistance, respectively. Supported by the National Institutes of Health (AI069259 and AI072252 to U.H.v.A.; HL07623 and Medical Scientist Training Program to S.E.H.; HL066987 to T.R.M.; PO1 AI071195-01 for H.Z., M.N.A. and A.K.C.).

Funding

We thank T. Buschman for assistance with programming; M. van den Broek for providing cDNA constructs for the P14 TCR; and G. Cheng and J. Alton for technical and secretarial assistance, respectively. Supported by the National Institutes of Health (AI069259 and AI072252 to U.H.v.A.; HL07623 and Medical Scientist Training Program to S.E.H.; HL066987 to T.R.M.; PO1 AI071195-01 for H.Z., M.N.A. and A.K.C.).

Funders	Funder number
Medical Scientist Training Program	HL066987, PO1 AI071195-01
National Institutes of Health	HL07623, AI069259, AI072252
National Institute of Allergy and Infectious Diseases	P01AI071195

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Henrickson, S. E., Mempel, T. R., Mazo, I. B., Liu, B., Artyomov, M. N., Zheng, H., Peixoto, A., Flynn, M. P., Senman, B., Junt, T., Wong, H. C., Chakraborty, A. K., & von Andrian, U. H. (2008). T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nature Immunology, 9(3), 282-291. https://doi.org/10.1038/ni1559

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title = "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.",

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

note = "Funding Information: We thank T. Buschman for assistance with programming; M. van den Broek for providing cDNA constructs for the P14 TCR; and G. Cheng and J. Alton for technical and secretarial assistance, respectively. Supported by the National Institutes of Health (AI069259 and AI072252 to U.H.v.A.; HL07623 and Medical Scientist Training Program to S.E.H.; HL066987 to T.R.M.; PO1 AI071195-01 for H.Z., M.N.A. and A.K.C.).",

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AU - Artyomov, Maxim N.

AU - Zheng, Huan

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AU - Flynn, Michael P.

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AU - Junt, Tobias

AU - Wong, Hing C.

AU - Chakraborty, Arup K.

AU - von Andrian, Ulrich H.

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N2 - 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.

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

Abstract

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