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PMID: 21205892 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 108 ·No. 4 ·2011-01-25 ·Pages 1549-54

Adachi K, Davis MM

Abstract

Naïve T lymphocytes display weaker and slower responses than antigen-experienced cells for reasons that are not well understood. Here we show that T-cell receptor (TCR) stimulation induces distinct ERK and p38 phosphorylation patterns in naïve and antigen-experienced human T cells, and that these contribute to the differential responses shown by these cells. Specifically, TCR ligation triggers the activation of the ERK pathway in naïve cells. This phosphorylation of ERK attenuates subsequent calcium influx and accelerates the degradation of the signalsome. In contrast, anti-CD3 stimulation of experienced cells results in the phosphorylation of p38 via an association with Discs large (Dlg). Thus, there are distinct signaling pathways triggered by TCR ligation that impair signaling in naïve cells and facilitate it in antigen-experienced cells.

MeSH Terms
Adaptor Proteins, Signal Transducing/metabolism Antigens/immunology Blotting, Western Butadienes/pharmacology CD4-Positive T-Lymphocytes/drug effects,immunology,metabolism CD8-Positive T-Lymphocytes/drug effects,immunology,metabolism Dendritic Cells/immunology,metabolism Discs Large Homolog 1 Protein Enterotoxins/immunology Enzyme Inhibitors/pharmacology Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors,metabolism Humans Imidazoles/pharmacology Interferon-gamma/metabolism Lymphocyte Activation/immunology Membrane Proteins/metabolism Nitriles/pharmacology Phosphorylation/drug effects Pyridines/pharmacology Receptors, Antigen, T-Cell/immunology Signal Transduction/immunology T-Lymphocytes/drug effects,immunology,metabolism p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Antigens Butadienes DLG1 protein, human Discs Large Homolog 1 Protein Enterotoxins Enzyme Inhibitors Imidazoles Membrane Proteins Nitriles Pyridines Receptors, Antigen, T-Cell U 0126 enterotoxin A, Staphylococcal Interferon-gamma Extracellular Signal-Regulated MAP Kinases p38 Mitogen-Activated Protein Kinases SB 203580
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Adachi Keishi
The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Davis Mark M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1017340108
Published
2011-01-25
Epub
2011-00-04
Pages
1549-54
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3029746
Subset
IM
Grants
NIAID NIH HHS · U19 AI057229 · United States
NIAID NIH HHS · U19 AI090019 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1073/pnas.1017340108 PMC Full Text View journal details
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