Question 4. How can a group AB individual produce an anti-A1 antibody?
N-acetylgalactosamine (GalNAc) is added to H antigen to create the A antigen. The A1 phenotype results from the "wild-type" A101 allele, which produces an enzyme capable of converting approximately 1,000,000 H antigens into A antigens. However, the A2 phenotype results from a non-sense mutation in the A101 allele, such that the translated enzyme contains 21 extra amino acids and is hypofunctional compared to the wild type A-synthesizing enzyme (see Figure 1 below). Less A antigens are created on A2 cells and an anti-A1 can be produced. Thus an AB individual with an anti-A1 in their serum is most likely A2B.