Balbino Alarcon

..Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling...

..Furthermore, we demonstrate for the first time that H-ras and N-ras act as critical controllers of Th1 responses, mostly by transmitting TCR signals for Th1 priming of CD4⁺ T cells...

..In this view, we discuss the participation of TC21 in the specific process of T cell antigen receptor internalization from the immunological synapse and acquisition of membrane fragments from the antigen presenting cells by phagocytosis...

..This finding, together with the known importance of Lck in the determination of CD4(+) and CD8(+) lineages, enables us to propose that a balance between the activation of these two kinases by the TCR determines lineage decisions...

..How the presence of TCR in clusters influences TCR avidity and propagation of TCR signals is something that has yet to be investigated...

..Here, we shall review the historical evolution of the role of the cSMAC in T-cell activation, finally discussing our most recent data indicating that the cSMAC serves to internalize exhausted TCRs by phagocytosis...

..Therefore, these results demonstrate that the TCR undergoes a conformational change on MHCp binding in vitro and in vivo, and they establish a molecular correlate for productive TCR engagement...

..Thus, the conformational change in the TCR may underlie the discrimination of ligands leading to positive and negative selection...

..Therefore, TC21 and RhoG dependence underlie the existence of a common phagocytic mechanism that drives TCR internalization from the IS together with its peptide-MHC ligand...

..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...

..These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome...

..Differences in the extent of PRS mutation could explain the phenotypic differences in both knockin mice...

..Thus, we propose that an "avidity maturation" mechanism underlies T cell antigenic memory...

..These results suggest that the pathway used for antigen uptake may modulate the antigen density presented on MHC-I, resulting in different signals induced in naïve CD8 T-cells, leading either to CD8 T-cell activation or anergy...

..These results emphasize the importance of the conformational change in CD3epsilon for the activation of T cells and suggest the existence of unforeseen cooperativity between TCR complexes...

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..Thus, besides resolving TCR stoichiometry, these data can explain how T cells respond to a wide range of MHCp concentrations while maintaining high sensitivity...

..Consequently, we propose TC21 directly links antigen receptors to PI(3)K-mediated survival pathways...

..The presence of EDAF improves the therapeutic potential of the CD4epsilon15 gene and it opens new possibilities for antiviral treatment and vaccine development...

..Taken together, these data demonstrate that CD3delta and CD3gamma play a different role in humans and mice in pre-TCR and TCR function during alphabeta T-cell development...

..In addition, Fyn deficiency significantly affects the MTOC relocation mediated by agonist peptide stimulation. These results reveal Fyn to be a key regulator of tubulin cytoskeleton reorganization in T cells...

..Finally, by interfering with Nck-CD3 epsilon association in vivo, we demonstrate that TCR-CD3 recruitment of Nck is critical for maturation of the immune synapse and for T cell activation...

..We propose that the stepwise assembly of the TCR complex guarantees that all assembly intermediates have at least one functional ER retention signal and that only a full signaling-competent TCR complex is expressed on the cell surface...