The Proline-Rich Sequence of Cd3 as an Amplifier of Low-Avidity Tcr Signaling

Tailor, P.; Tsai, S.; Shameli, A.; Serra, P.; Wang, J.; Robbins, S.; Nagata, M.; Szymczak-Workman, A.L.; Vignali, D.A.A.; Santamaria, P.

The Journal of Immunology 181(1): 243-255


DOI: 10.4049/jimmunol.181.1.243
Accession: 068491038

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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.