Biochemistry and Biosynthesis of ABH and Lewis Antigens

Abstract

Serological techniques were used initially to define the human ABO, H, and Lewis blood group determinants. These studies were done in the context of exploring genetic polymorphisms in the expression of such antigens, usually identified in association with antibody-mediated red blood cell destruction occurring after blood transfusion. Following the studies that uncovered these determinants earlier in this century, a substantial amount of experimental effort was expended to determine the precise structural nature of these molecules, and the genetic and molecular basis for their polymorphic properties. We now have a detailed picture of the chemical nature of these blood group determinants, we understand their biosynthetic pathways in substantial detail, and recent work has yielded a satisfyingly consistent set of hypotheses concerning the genes and enzymes that determine their expression. As will be detailed below, and in Chapter 2 of this volume, the molecules of the A, B, H, and Lewis blood group determinants are oligosaccharides, which are constructed by the sequential catalytic action of glycosyltransferase enzymes. Recent studies in this area have been focused on isolating and characterizing such glycosyltransferase genes. As will be apparent below, the genes corresponding to the ABO, H, and Lewis blood group loci have been cloned and characterized. Moreover, recent work suggests that the human Secretor blood group locus has also been isolated. These cloned gene segments represent tools for characterizing the molecular basis for genetic polymorphisms in these loci, and for defining the basis for the tissue-specific expression patterns of these oligosaccharide-type antigens, at the molecular level.