Carbohydrates as antigenic determinants of glycoproteins.

Antibodies are being used increasingly as reagents in biochemical and biological studies of glycoproteins, for example, in the search for glycoproteins with important roles in embryonic development, cell differentiation and oncogenesis, and as a means of monitoring the biosynthesis and subcellular location of specific glycoproteins such as enzymes and receptors. Crucial for the proper application of antibodies in such experiments is knowledge of the determinants they recognize. A glycoprotein may contain many antigenic determinants, each consisting ofup to seven monosaccharides or amino acids in consecutive sequence (Kabat, 1976) or, in the case of polypeptides, in non-continuous sequence brought together by chain folding (Lerner, 1984; Walter, 1986). Unravelling the specificities contained in conventional (polyclonal) antisera raised against glycoproteins often presents problems due to the mixture of antibodies present with different combining specificities. It is often difficult to distinguish specificities directed against peptide determinants from those directed against carbohydrate structures on a glycoprotein. Monoclonal antibodies have the advantage in this respect since each is a single antibody population with a narrow specificity. As a result ofwork with naturally-occurring monoclonal autoantibodies and the widespread use of hybridomaderived antibodies, there has been an increased awareness of carbohydrates as antigenic determinants of glycoproteins, since it has become apparent that many differentiation antigens ofnormal and neoplastic cells are oligosaccharide determinants of glycoproteins and glycolipids rather than peptide determinants (Feizi, 1985, 1987; Hakomori, 1985). Thus, carbohydrate antigens which were previously the interest of specialist immunochemists are now of wide relevance to both biochemists and cell biologists. We do not intend here to make an exhaustive review of antigens found to date on glycoprotein oligosaccharides; rather we shall discuss some examples of whole cells (haematopoietic and embryonic) and specific glycoproteins (a receptor and a glycosyltransferase) where carbohydrate structures have been found to be major antigenic determinants. We shall also discuss approaches to the study of antigenicity (reactivity with antibodies) and immunogenicity (ability to elicit antibodies) of the oligosaccharides of glycoproteins and the opportunities now available for exploiting antibodies with defined carbohydrate specificities as probes of the structure, tissue distribution and function of glycoprotein oligosaccharides. We also include in this article a hypothesis which considers the biological relevance and possible inter-relationships of three areas of knowledge: (a) the occurrence of the same carbohydrate antigens/structures on diverse and unrelated glycoproteins, (b) marked