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.
Julia McFarlane Diabetes Research Centre and Department of Microbiology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Pankaj
P
Tailor
Sue
S
Tsai
Afshin
A
Shameli
Pau
P
Serra
Jinguo
J
Wang
Stephen
S
Robbins
Masao
M
Nagata
Andrea L
AL
Szymczak-Workman
Dario A A
DA
Vignali
Pere
P
Santamaria
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