pMHC affinity controls duration of CD8+ T cell-DC interactions and imprints timing of effector differentiation versus expansion.

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Version: Final published version
Serval ID
serval:BIB_9948D26FD645
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
pMHC affinity controls duration of CD8+ T cell-DC interactions and imprints timing of effector differentiation versus expansion.
Journal
The Journal of experimental medicine
Author(s)
Ozga A.J., Moalli F., Abe J., Swoger J., Sharpe J., Zehn D., Kreutzfeldt M., Merkler D., Ripoll J., Stein J.V.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
14/11/2016
Peer-reviewed
Oui
Volume
213
Number
12
Pages
2811-2829
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
During adaptive immune responses, CD8(+) T cells with low TCR affinities are released early into the circulation before high-affinity clones become dominant at later time points. How functional avidity maturation is orchestrated in lymphoid tissue and how low-affinity cells contribute to host protection remains unclear. In this study, we used intravital imaging of reactive lymph nodes (LNs) to show that T cells rapidly attached to dendritic cells irrespective of TCR affinity, whereas one day later, the duration of these stable interactions ceased progressively with lowering peptide major histocompatibility complex (pMHC) affinity. This correlated inversely BATF (basic leucine zipper transcription factor, ATF-like) and IRF4 (interferon-regulated factor 4) induction and timing of effector differentiation, as low affinity-primed T cells acquired cytotoxic activity earlier than high affinity-primed ones. After activation, low-affinity effector CD8(+) T cells accumulated at efferent lymphatic vessels for egress, whereas high affinity-stimulated CD8(+) T cells moved to interfollicular regions in a CXCR3-dependent manner for sustained pMHC stimulation and prolonged expansion. The early release of low-affinity effector T cells led to rapid target cell elimination outside reactive LNs. Our data provide a model for affinity-dependent spatiotemporal orchestration of CD8(+) T cell activation inside LNs leading to functional avidity maturation and uncover a role for low-affinity effector T cells during early microbial containment.

Keywords
Animals, Antigens, CD/metabolism, Antigens, Differentiation, T-Lymphocyte/metabolism, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/immunology, Cell Communication/immunology, Cell Differentiation/immunology, Cell Proliferation, Cross-Priming/immunology, Cytotoxicity, Immunologic, Dendritic Cells/cytology, Dendritic Cells/immunology, Gene Expression Regulation, Granzymes/metabolism, Image Processing, Computer-Assisted, Lectins, C-Type/metabolism, Lymph Nodes/immunology, Lymphatic Vessels/metabolism, Major Histocompatibility Complex/immunology, Mice, Inbred C57BL, Peptides/immunology, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, Virus Diseases/immunology
Pubmed
Web of science
Open Access
Yes
Create date
29/11/2016 14:39
Last modification date
20/08/2019 15:00
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