Almost thirty years ago the long sought-after receptor for antigen and MHC on T cells (TCR) was discovered. Enormous progress has since been made towards the understanding of TCR structure, intracellular signaling machinery and functional programs induced by its stimulation.
Curiously, however, we are still searching for a satisfactory model that explains how TCR binding to peptide/MHC is converted across the cell membrane into physical and/or chemical changes that trigger the signaling cascade. Various mechanisms invoking allosteric-, membrane domain-, oligomerization-, co-receptor-, dimension-, mechano-dependent triggering have been proposed, some of which may not be mutually exclusive but rather represent temporally distinct phases of a complex process. This wealth of TCR triggering models echoes the "unconventional" structure and functioning of the TCR and its associated signaling machinery, to guarantee that T cells translate unpredictable peptide/MHC stimuli into adequate choices that preserve tissue and organ integrity.
The immunologist community greatly welcomes a timely series of original articles, reviews, and opinion-viewpoints on “how TCR signaling begins”. This is meant to generate discussion, clarification and consensus and help conceiving better designed/more advanced experiments to provide a cogent answer to these uncertainties.
Almost thirty years ago the long sought-after receptor for antigen and MHC on T cells (TCR) was discovered. Enormous progress has since been made towards the understanding of TCR structure, intracellular signaling machinery and functional programs induced by its stimulation.
Curiously, however, we are still searching for a satisfactory model that explains how TCR binding to peptide/MHC is converted across the cell membrane into physical and/or chemical changes that trigger the signaling cascade. Various mechanisms invoking allosteric-, membrane domain-, oligomerization-, co-receptor-, dimension-, mechano-dependent triggering have been proposed, some of which may not be mutually exclusive but rather represent temporally distinct phases of a complex process. This wealth of TCR triggering models echoes the "unconventional" structure and functioning of the TCR and its associated signaling machinery, to guarantee that T cells translate unpredictable peptide/MHC stimuli into adequate choices that preserve tissue and organ integrity.
The immunologist community greatly welcomes a timely series of original articles, reviews, and opinion-viewpoints on “how TCR signaling begins”. This is meant to generate discussion, clarification and consensus and help conceiving better designed/more advanced experiments to provide a cogent answer to these uncertainties.
