|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
35
|
|
pubmed:dateCreated |
2010-9-2
|
|
pubmed:abstractText |
The size and sensitivity of the T-cell repertoire governs the effectiveness of immune responses against invading pathogens. Both are modulated by T-cell receptor (TCR) activity through molecular mechanisms, which remain unclear. Here, we provide genetic evidence that the SH2/SH3 domain containing proteins Nck lower the threshold of T-cell responsiveness. The hallmarks of Nck deletion were T-cell lymphopenia and hyporeactivity to TCR-mediated stimulation. In the absence of the Nck adaptors, peripheral T cells expressing a TCR with low avidity for self-antigens were strongly reduced, whereas an overall impairment of T-cell activation by weak antigenic stimulation was observed. Mechanistically, Nck deletion resulted in a significant decrease in calcium mobilization and ERK phosphorylation upon TCR engagement. Taken together, our findings unveil a crucial role for the Nck adaptors in shaping the T-cell repertoire to ensure maximal antigenic coverage and optimal T cell excitability.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
1091-6490
|
|
pubmed:author |
pubmed-author:ArnoldBerndB,
pubmed-author:BladtFriedhelmF,
pubmed-author:HämmerlingGünterG,
pubmed-author:HoldorfAmy DAD,
pubmed-author:KüblbeckGünterG,
pubmed-author:KlevenzAlexandraA,
pubmed-author:Kopp-SchneiderAnnetteA,
pubmed-author:LeithäuserFrankF,
pubmed-author:MöllerPeterP,
pubmed-author:NabtiSabrinaS,
pubmed-author:PawsonTonyT,
pubmed-author:RoyEdwigeE,
pubmed-author:TafuriAnnaA,
pubmed-author:TogbeDieudonnéeD,
pubmed-author:TrubetskoyDmitryD
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
31
|
|
pubmed:volume |
107
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
15529-34
|
|
pubmed:meshHeading |
pubmed-meshheading:20709959-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:20709959-Animals,
pubmed-meshheading:20709959-Blotting, Western,
pubmed-meshheading:20709959-Calcium,
pubmed-meshheading:20709959-Cell Proliferation,
pubmed-meshheading:20709959-Cells, Cultured,
pubmed-meshheading:20709959-Dendritic Cells,
pubmed-meshheading:20709959-Female,
pubmed-meshheading:20709959-Flow Cytometry,
pubmed-meshheading:20709959-Lymphopenia,
pubmed-meshheading:20709959-Male,
pubmed-meshheading:20709959-Mice,
pubmed-meshheading:20709959-Mice, Inbred C57BL,
pubmed-meshheading:20709959-Mice, Knockout,
pubmed-meshheading:20709959-Microscopy, Fluorescence,
pubmed-meshheading:20709959-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:20709959-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:20709959-Oncogene Proteins,
pubmed-meshheading:20709959-Phosphorylation,
pubmed-meshheading:20709959-Receptors, Antigen, T-Cell,
pubmed-meshheading:20709959-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20709959-T-Lymphocytes
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Nck adaptors are positive regulators of the size and sensitivity of the T-cell repertoire.
|
|
pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale, Institut Curie, 75005 Paris, France.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
