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PMID: 18204450 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Nature immunology ·Vol. 9 ·No. 3 ·2008-03-00 ·Pages 282-91

Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN, Zheng H, Peixoto A, Flynn MP, Senman B, Junt T, Wong HC, Chakraborty AK, von Andrian UH

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.

MeSH Terms
Animals Antigen-Presenting Cells/immunology Antigens, Surface/genetics,metabolism Cells, Cultured Dendritic Cells/immunology,metabolism Dose-Response Relationship, Immunologic Kinetics Lymphocyte Activation/immunology Major Histocompatibility Complex/immunology Male Mice Mice, Inbred C57BL Peptide Fragments/genetics T-Lymphocytes/immunology,metabolism
Chemicals
Antigens, Surface Peptide Fragments
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Henrickson Sarah E
Department of Pathology and the Immune Disease Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mempel Thorsten R
Mazo Irina B
Liu Bai
Artyomov Maxim N
Zheng Huan
Peixoto Antonio
Flynn Michael P
Senman Balimkiz
Junt Tobias
Wong Hing C
Chakraborty Arup K
von Andrian Ulrich H
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni1559
Published
2008-03-00
Epub
2008-00-20
Pages
282-91
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2698867
Subset
IM
Grants
NHLBI NIH HHS · T32 HL066987 · United States
NCI NIH HHS · P01 CA071932 · United States
NIGMS NIH HHS · T32 GM007753 · United States
NIAID NIH HHS · P01 AI071195-01 · United States
NIAID NIH HHS · AI069259 · United States
NIAID NIH HHS · P01 AI071195 · United States
NIAID NIH HHS · R01 AI072252 · United States
NIAID NIH HHS · R01 AI069259 · United States
NCI NIH HHS · P01 CA071932-11A2 · United States
NHLBI NIH HHS · HL066987 · United States
NHLBI NIH HHS · T32 HL007623 · United States
NIAID NIH HHS · AI072252 · United States
NHLBI NIH HHS · HL07623 · United States
Corrections
CommentIn
PMID: 18285771
External Links
PubMed source DOI: 10.1038/ni1559 PMC Full Text View journal details
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