Structural and evolutionary analysis of HLA-D-region products.

Journal article

The major histocompatibility complex (MHC)--HLA in man and H-2 in mouse--encodes two classes of cell-surface antigens involved in the immune response. The amino acid sequences have been determined for a number of these molecules. Class I antigens, typified by the HLA-ABC antigens, are composed of a 43,000-molecular weight (MW) glycosylated transmembrane polypeptide with three external domains (alpha 1, alpha 2 and alpha 3), of which the one nearest the membrane (alpha 3) is associated with a 12,000-MW nonglycosylated polypeptide, beta 2-microglobulin. The HLA-D-region or class II antigens, DR, DC and SB, are composed of two glycosylated transmembrane polypeptides, of MWs 34,000 (alpha-chain) and 28,000 (beta-chain). Both chains have two external domains which presumably associate with each other, alpha 2, beta 2 being membrane proximal and alpha 1, beta 1 N-terminal and membrane distal. All four membrane-proximal domains (class I alpha 3, beta 2-microglobulin, class II alpha 2 and beta 2) have amino acid sequences that show significant similarities with immunoglobulin constant-region domains. This, together with the similarly placed internal disulphide bonds, suggests they might have an immunoglobulin-like structure (Fig. 1). We have now used computer graphics techniques to predict a detailed three-dimensional structure for the membrane-proximal domains of the class II antigens (alpha 2 and beta 2) based on the known coordinates of immunoglobulin constant domains (Fig. 2). The transmembrane regions of class II antigens have been modelled as two alpha-helices packed together. The proposed structure accounts for conservation of amino acids and leads to evolutionary predictions.

Authors: Travers, P; Blundell, T; Sternberg, M; Bodmer, W

• Publication status: Published
• Journal: Nature
• Volume: 310
• Issue: 5974
• Pages: 235-238
• Publication date: 1984-01-01
• DOI: 10.1038/310235a0
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Biological Evolution; HLA-DQ Antigens; Histocompatibility Antigens Class II; HLA-DR Antigens; Amino Acid Sequence; Humans; Membrane Proteins; HLA-B7 Antigen; beta 2-Microglobulin; Protein Conformation; Animals; HLA Antigens; HLA-DP Antigens; Immunoglobulin Constant Regions; Immunoglobulin Fab Fragments; Macromolecular Substances; Mice