On the molecular nature of "restrictive" antigenic elements present on major histocompatibility complex (MHC)...

By analogy with the way in which antibodies recognize their specific antigens, it appears likely that T-cell receptors recognize peptides presented by MHC molecules as composite epitopes involving the presented peptide and portions of the MHC molecules. We extend here the analogy to attempt to define which portions of the MHC molecules are most accessible to the TcR and thereby most likely to participate in the binding. We suggest that the alpha chain segments 56-60, 73-77, 149-153 and 158-162, which are most protruding according to accessibility calculations, are likely candidates for the interaction. Again, by analogy with antibodies, we further propose that TcR recognition may involve: (1) an "active" recognition process, focussed on a few residues which provide the major contribution to the binding energy, and (2) a "passive" recognition process, in which the relatively large contact areas between TcR and the composite epitope primarily need to be compatible with one another rather than to contribute significantly to binding energy.