(A) Structure of monomeric IgA1 and its hinge region in comparison with IgA2 (A2m(l) allotype) (36). The IgA1 hinge region consists of a short amino acid sequence between CH1 and CH2 of the α1 heavy chain. In contrast to IgA2, the IgA1 hinge region contains two octapeptide repeats composed of Ser, Thr, and proline (Pro) residues (arrows). Of the nine potential Ser and Thr O-glycosylation sites, three to six are usually occupied (numbered Ser/Thr residues) (25–29). (B) Biosynthesis of hinge-region O-glycans of human circulatory IgA1. The possible structures of O-glycans in the hinge region of IgA1 include GalNAc with galactose that may contain up to two N-acetylneuraminic acid residues. Galactose-deficient glycans include terminal or sialylated GalNAc. Enzymes catalyzing the specific steps in this pathway are shown.