Open AccessThe Proline-Rich Sequence of CD3ε as an Amplifier of Low-Avidity TCR Signaling
Author(s) -
Pankaj Tailor,
Sue Tsai,
Afshin Shameli,
Pau Serra,
Jinguo Wang,
Stephen M. Robbins,
Masao Nagata,
Andrea L. Szymczak-Workman,
Dario A.A. Vignali,
Pere Santamaría
Publication year - 2008
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.181.1.243
Subject(s) - biology , t cell receptor , avidity , phosphorylation , microbiology and biotechnology , cd8 , immunological synapse , signal transducing adaptor protein , t cell , immune system , antigen , genetics
Engagement of peptide-MHC by the TCR induces a conformational change in CD3epsilon that exposes a proline-rich sequence (PRS) and recruits the cytoskeletal adaptor Nck. This event, which precedes phosphorylation of the CD3epsilon ITAM, has been implicated in synapse formation and T cell function. However, there is compelling evidence that responsiveness to TCR ligation is CD3epsilon PRS independent. In this study, we show that the CD3epsilon PRS is necessary for peptide-MHC-induced phosphorylation of CD3epsilon and for recruitment of protein kinase Ctheta to the immune synapse in differentiated CD8+ T lymphocytes. However, whereas these two events are dispensable for functional T cell responsiveness to high-avidity ligands, they are required for responsiveness to low-avidity ones. Thus, in at least certain T cell clonotypes, the CD3epsilon PRS amplifies weak TCR signals by promoting synapse formation and CD3epsilon phosphorylation.
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