The Functional Significance of Amino Acid Polymorphisms in Class I MHC Molecules

Abstract

The x-ray crystal model of the HLA-A2 molecule depicts an antigen presenting domain consisting of two α-helices under which are found eight antiparallel β-strands. Furthermore, the position, orientation, and functional contribution of many amino acid side chains has been proposed (Björkman 1987a,b). In general, amino acid residues that point inward/upward from the α-helices or point upward from the β-strand floor are thought to be involved with either peptide binding or T-cell receptor (TcR) interaction. Amino acid side chains that point outward from the α-helices, project downward from the β-strand floor, or are located on loops outside of the antigen recognition site (ARS) are thought to be silent with regard to TcR interaction or peptide binding (Björkman 1987b).