Structure of Human Major Histocompatibility Complex Class II Genes

Abstract

Class II histocompatibility antigens, which are encoded by the Major histocompatibility complex (HLA in man) are expressed mainly by cells belonging to the immune system. They are composed of two dissimilar protein chains, both spanning the cell membrane. The two chains, denoted α and β, and with approximate m.w. of 35,000 and 28,000, respectively, interact non-covalently. The extra-cellular portion of each chain is composed of two domains, each consisting of approximately 90 amino acid residues. A stretch of approximately 20 hydrophobic or non-charged amino acid residues spans the cell membrane. On the cytoplasmic side of the cell membrane fairly short peptide segments are located, composed of 10 to 22 residues. The membrane-proximal domain (2nd domain) of the two chains displays sequence similarity to immunoglobulin constant domains, whereas the amino-terminal domain (1st domain) lacks this similarity. A salient feature of class II antigens is their polymorphism. The amino acid replacements, which create the corresponding sequence variability, are almost exclusively located in the 1st domain of the β chain and in some isotypes of class II antigens also in the 1st domain of the α chain (Rask et al. 1985). A schematic picture of a class II molecule and its corresponding genes is shown in Fig. 1.