Biochemistry of H, A, & B antigen

 

Biosynthesis of the H, A and B antigens involves a series of enzymes (glycosyl transferases) that transfer monosaccharides.

• The resulting antigens are oligosaccharide chains, which are attached to lipids and proteins that are anchored in the red blood cell membrane. The function of the H antigen, apart from being an intermediate substrate in the synthesis of ABO blood group antigens, is not known, although it may be involved in cell adhesion.

• People who lack the H antigen do not suffer from deleterious effects, and being H-deficient is only an issue if they need a blood transfusion, because they would need blood without the H antigen present on red blood cells.

• The specificity of the H antigen is determined by the sequence of oligosaccharides. More specifically, the minimum requirement for H antigenicity is the terminal disaccharide fucose-galactose, where the fucose has an alpha(1-2)linkage. This antigen is produced by a specific fucosyl transferase that catalyzes the final step in the synthesis of the molecule.

 
• Depending upon a person's ABO blood type, the H antigen is converted into either the A antigen, B antigen, or both. If a person has group O blood, the H antigen remains unmodified. Therefore, the H antigen is present more in blood type O and less in blood type AB.

• Hh antigen system - diagram showing the molecular structure of the ABO(H) antigen system.

• Two regions of the genome encode two enzymes with very similar substrate specificities: the H locus (FUT1) which encodes the Fucosyl transferase and the Se locus (FUT2) that instead indirectly encodes a soluble form of the H antigen, which is found in bodily secretions. Both genes are on chromosome 19 at q.13.3. - FUT1 and FUT2 are tightly linked, being only 35 kb apart. Because they are highly homologous, they are likely to have been the result of a gene duplication of a common gene ancestor.