Nck Adaptors Are Positive Regulators of the Size and Sensitivity of the T-cell Repertoire

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Aug 17

PMID 20709959

Citations 16

Authors

Edwige Roy

Dieudonnee Togbe

Amy D Holdorf

Dmitry Trubetskoy

Sabrina Nabti

Gunter Kublbeck

Alexandra Klevenz

Annette Kopp-Schneider

Frank Leithauser

Peter Moller

Friedhelm Bladt

Gunter Hammerling

Bernd Arnold

Tony Pawson

Anna Tafuri

Affiliations

Soon will be listed here.

Abstract

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.

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