t cell receptor engagement triggers its cd3ε and cd3ζ subunits to adopt a compact, locked conformationt细胞受体参与触发cd3ε和cd3ζ子单元采用紧凑,锁定构象.pdfVIP

T Cell Receptor Engagement Triggers Its CD3e and CD3f Subunits to Adopt a Compact, Locked Conformation ˜ 1 2 ´ 1 Ruth M. Risueno , Wolfgang W. A. Schamel , Balbino Alarcon * ´ ´ ´ ¨ 1 Centro de Biologıa Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientıficas, Universidad Autonoma de Madrid, Madrid, Spain, 2 Max Planck-Institut fur Immunbiologie, Freiburg, Germany Abstract 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 CD3e 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 CD3e and CD3f subunits become fully protected from degradation upon TCR triggering. These results suggest that the TCR conformational change is transmitted to the tails of CD3e and CD3f, 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