T cell receptor engagement triggers its CD3epsilon and CD3zeta subunits to adopt a compact, locked conformation.
How the T cell antigen receptor (TCR) discriminates between molecularly related peptide/Major Histocompatibility Complex (pMHC) ligands and converts this information into different possible signaling outcomes is still not understood. One current model proposes that strong pMHC ligands, but not weak ones, induce a conformational change in the TCR. Evidence supporting this comes from a pull-down assay that detects ligand-induced binding of the TCR to the N-terminal SH3 domain of the adapter protein Nck, and also from studies with a neoepitope-specific antibody. Both methods rely on the exposure of a polyproline sequence in the CD3epsilon subunit of the TCR, and neither indicates whether the conformational change is transmitted to other CD3 subunits. Using a protease-sensitivity assay, we now show that the cytoplasmic tails of CD3epsilon and CD3zeta subunits become fully protected from degradation upon TCR triggering. These results suggest that the TCR conformational change is transmitted to the tails of CD3epsilon and CD3zeta, and perhaps all CD3 subunits. Furthermore, the resistance to protease digestion suggests that CD3 cytoplasmic tails adopt a compact structure in the triggered TCR. These results are consistent with a model in which transduction of the conformational change induced upon TCR triggering promotes condensation and shielding of the CD3 cytoplasmic tails.
Risueño
Ruth M
RM
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
Schamel
Wolfgang W A
WW
Alarcón
Balbino
B
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008285:Major Histocompatibility Complex / Q000502:physiology; D015513:Oncogene Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011487:Protein Conformation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C115335:CD3E protein, human; C078332:Nck protein; D015513:Oncogene Proteins; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell