The proline-rich sequence of CD3epsilon as an amplifier of low-avidity TCR signaling.
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.
Tailor
Pankaj
P
Julia McFarlane Diabetes Research Centre and Department of Microbiology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Tsai
Sue
S
Shameli
Afshin
A
Serra
Pau
P
Wang
Jinguo
J
Robbins
Stephen
S
Nagata
Masao
M
Szymczak-Workman
Andrea L
AL
Vignali
Dario A A
DA
Santamaria
Pere
P
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005784:Gene Amplification / Q000235:genetics*; D006649:Histocompatibility Antigens / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D010766:Phosphorylation; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D017252:CD3 Complex; D006649:Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011392:Proline; D011493:Protein Kinase C