Serology, genetics and chemistry of the MNS blood group system

The MNSs blood group gene locus apparently corresponds to two adjacent and homologous genes which code for the amino acid sequences of two (MN and Ss) erythrocyte membrane sialoglycoproteins. The genes En, u and Mk represent alleles, silent at one or the other and at both loci, respectively. Amino acid polymorphisms at the first (Ser/Leu) and fifth (Gly/Glu) positions of the major (MN) glycoprotein account for the structural difference between the MN antigens. The N-terminal 26 residues of the Ss glycoprotein are completely identical with those of the blood group N-specific major glycoprotein, providing an explanation for the additional N receptor, denoted as 'N', on this molecule. A Met/Thr polymorphism at position 29 of the Ss glycoprotein represents the structural difference between the Ss antigens, as revealed by chemical modification experiments and sequence analysis. The Ux polymorphism, defined by a scarce serum (anti-Ux) directed against receptors within the homologous domains of the two glycoproteins, appears to be caused by differences in the Ss glycoprotein content between SS, Ss and ss red cells, rather than by an additional structural polymorphism on the Ss glycoprotein. The same explanation might also account for a further (Uz) polymorphism, defined by anti-Uz reacting with receptors which are located on a more interior portion of this molecule. Various factors such as the number of receptors per cell, their accessibility within the intact erythrocyte membrane as well as properties of the antibody (Uu genotype of the donor, method of absorption, the number of sites per antibody and its binding constant) contribute to the phenomenon that the capacity for reaction of the structurally identical N and 'N' antigens in intact red cells is different, thus enabling MN blood typing, despite the presence of 'N' receptors in MM erythrocytes.