Theoretical studies of transplantation antigens: Predicted conformation and structure-function relationship of the murine MHC class i antigen H-2Kb

Despite the elucidation of the primary sequences of a number of transplantation antigens from human and murine sources, no tertiary structure has yet been determined. In an attempt to determine a theoretically-stable spatial conformation for the heavy chain and the β₂-microglobulin, which constitute the murine class I transplantation antigen H-2K^b, a computer program has been used. This program, developed by us, searches for the preferred conformations of proteins, under an energy criterion, through variation of the dihedral angles Φ,Ψ,χ,₁. A stable conformation of the complex formed by both chains was then obtained, also under an energy criterion, by means of a molecular interactions program developed in this laboratory. The information obtained from the resulting structure (spatial distribution of the residues and helical content), together with complementary information from the hydrophilicity and recognition profiles of the heavy chain, suggest that the sequence regions 63–72 and 129–139 constitute the alloantigenic determinants of H2K^b. The fact that the 63–72 region is an alloantigenic determinant has been confirmed by the use of a synthetic peptide 61–69, which elicits specific T and B cell immune responses against the H-2K^b molecule.