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There is considerable controversy about the mechanism of T cell receptor (TCR) triggering, the process by which the TCR tranduces signals across the plasma membrane after binding to its ligand (an agonist peptide complexed with an MHC molecule). Three main types of mechanism have been proposed, which involve aggregation, conformational change and segregation. Here, we review recently published evidence for each type of mechanism and conclude that all three may be involved. This complexity may reflect the uniquely demanding nature of TCR-mediated antigen recognition, which requires the detection of a very weak 'signal' (very rare foreign peptide-MHC ligands) in the presence of considerable 'noise' (abundant self peptide-MHC molecules).

Original publication




Journal article


Nat Rev Immunol

Publication Date





47 - 55


Animals, Antigen-Presenting Cells, CD3 Complex, Humans, Lymphocyte Activation, Major Histocompatibility Complex, Mice, Protein Binding, Receptors, Antigen, T-Cell