The CD3epsilon proline-rich sequence, and its interaction with Nck, is not required for T cell development and function.
The CD3epsilon proline-rich sequence (PRS) binds to the cytosolic adaptor molecule Nck after TCR ligation. It has been proposed that this interaction is essential for immunological synapse formation and T cell activation. To assess the physiological importance of the CD3epsilon PRS, we have generated mice that lack this motif (CD3epsilon.PRS(M)). Pull-down experiments demonstrated the inability of Nck to bind to the CD3epsilon PRS in thymocytes from mutant mice after TCR ligation. Surprisingly, no differences were observed in the number and percentage of T cell subsets in the thymus and spleen, and there was no apparent defect in positive or negative selection. Furthermore, the proliferative response of CD3epsilon.PRS(M) T cells to staphylococcal enterotoxin B and anti-CD3 Ab was normal. TCR surface expression, constitutive internalization, and Ag-induced down-modulation were also normal. These data suggest that the interaction between the CD3epsilon PRS and Nck, or any other Src homology 3 domain-containing molecule, is not essential for T cell development and function.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Andrea L
AL
Szymczak
Creg J
CJ
Workman
Diana
D
Gil
Smaroula
S
Dilioglou
Kate M
KM
Vignali
Ed
E
Palmer
Dario A A
DA
Vignali
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017252:CD3 Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism*; D011392:Proline / Q000737:chemistry; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; C485468:Cd3e protein, mouse; C078332:Nck protein; D015513:Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D011392:Proline