T‐Cell Recognition of Antigen

As recently as ten years ago, the nature of the T-cell receptor for antigen was a mystery, as was the precise role of histocompatibility molecules in antigen-presentation to T cells. Although T-cell receptors have now been cloned and crystal structures of MHC/peptide molecules exist, our understanding of the parameters that characterize this interaction and other interactions relevant to T-cell immunity are still unclear. The engineering of soluble forms of proteins that mediate T-cell recognition of antigen has allowed the first measurements of these parameters. Interestingly, many of these interactions are of a transient nature, with very rapid off-rates. These data suggest a model whereby highly reversible intermolecular interactions mediate the cell-cell association. The association of adhesion molecules is probably the first step in the stabilization of a conjugate, because they are more numerous than any antigen-specific interaction, followed later by TCR-MHC engagements. Diffusion within each lipid bilayer should allow the congregation of MHC/TCR interactions at the cell-cell interface, with peptide-specific TCR interactions outcompeting irrelevant interactions. Rapid off-rates for both the antigen-specific and nonspecific interactions may be necessary to maintain reversibility, yet allow a rapid approach to equilibrium and consequent signaling when a specific antigen is present or disengagement when it is not.