Structure and function of red cell surface antigens

Abstract

Currently there are almost 300 red cell surface antigenic determinants or blood group specificities recognized by the International Society of Blood Transfusion; most of these belong to 1 of 29 blood group systems. Each system represents a single gene or cluster of 2 or 3 closely linked homologous genes, giving a total of 34 gene loci. Each of these genes has been cloned and sequenced, with the exception of one, P , and there is a candidate gene for this. Consequently, we have a tremendous amount of structural information about the red cell surface. Despite this, there is still much we do not know about the functions of these antigens; much of what we do know has been deduced from their structures. We know almost nothing about the functions of the blood group polymorphisms. The blood group systems are listed in Table 1, with information on the structures of their antigens and their possible functions. Almost all blood group systems have a null phenotype, in which no antigen of that system is expressed on the red cells. Null phenotypes are generally rare. They are usually only found when individuals with these phenotypes may make antibodies to the missing proteins following immunization by blood transfusion or pregnancy. Such antibodies are then identified in immunohaematology reference laboratories. Null phenotypes usually result from homozygosity for inactivating mutations or even a gene deletion, so the whole protein is absent from the red cells and from everywhere else in the body, at any stage of development. Yet in many cases individuals with these rare phenotypes are apparently healthy. This reflects the functional redundancy of many cell surface proteins. Often, when one protein is missing, another can perform the same function in its absence. However, this is not always the case and null phenotypes have been very informative about the functions of blood group antigens both on red cells and in other tissues. Red cell surface antigens are macromolecules anchored in the lipid bilayer of the red cell envelope. There are three main types of macromolecules expressing blood group activity: proteins, glycoproteins, and glycolipids. Most blood group antigens are glycoproteins, with the specificity determined primarily either by the oligosaccharide sequence (e.g. ABO) or by the amino acid sequence (e.g. MN, Kell, Duffy, Kidd, Diego). The Rh antigens are non-glycosylated proteins, though the presence of an associated glycoprotein is required for antigenic expression. ABO antigens are also expressed on the carbohydrate moiety of glycosphingolipids. In this article red cell surface antigens will be discussed in terms of their functions or potential functions, under the following five headings: transporters and channels; receptors and adhesion molecules; enzymes; structural proteins that link the lipid bilayer to the membrane skeleton; and those structures that contribute to the glycocalyx, or cell coat.