[HLA-DR antigens: cellular expression and molecular structure].

Abstract

The HLA complex encodes several sets of membrane glycoproteins with extensive genetic, functional and structural polymorphism. The HLA-D region and its products, the HLA-DR antigens, are central in immune phenomena. They control the mixed lymphocyte reaction, the graft versus host reaction in vivo and cell/cell interactions involved in immune responses. Monoclonal anti HLA-DR antigens have been used to investigate the expression and synthesis of human Ia antigens on B and active T lymphocytes and macrophages. They were subsequently used in structural studies of HLA-DR antigens analysed by two-dimensional gel electrophoresis. The HLA-DR antigens are composed of a bimolecular complex of two non-covalently linked subunits: a 34,000 dalton alpha chain and a 29,000 dalton beta chain. Glycosylation steps and molecular maturation include the addition of oligosaccharides and sialic acid residues to the native polypeptide chain. The structural polymorphism which correlates with the serologically defined HLA-DR determinants is localized on the beta chain and is of polypeptidic origin. A third component of the HLA-DR antigen is described: the 31,000-dalton "invariant" chain. Its peptide composition, glycosylation pattern and expression are reported. Homologies of HLA-DR antigens with the mouse Ia antigens are discussed. Structural studies of the human Ia system are important in dissecting the functional role of the different epitopes of the HLA-DR molecules.