Putting a Face to MHC Restriction

It is now an immunological fact that small peptides bound to polymorphic MHC molecules are the antigenic ligands recognized by � � TCRs. All of protective immunity is built from and fueled by these interactions, as are the chronic diseases of autoimmunity and hypersensitivity that afflict affluent society. Through positive and negative selection in the thymus, self peptides bound to autologous MHC molecules determine the repertoire of peripheral T cells, which then responds to infection by recognizing foreign peptides bound to those same MHC molecules. In looking back, the erratic voyage of serendipity that was made to discover this fact—-now said in a sentence—-involved a century of exploration and adventure. For those on board in 1987, two papers by Bjorkman et al. in the October 8–14 issue of Nature magazine gave a first sighting of the journey’s end. The first paper was an immunologist’s guide to the three-dimensional structure of the human MHC class I molecule, HLA-A2 (1); the second paper was a manifesto, laying out the implications of the structure for T cell biology (2).