Struktura i funkcja podklas immunoglobuliny klasy A

Abstrakt

Summary An unusual structural feature of human immunoglobulin A (IgA) is the heterogeneity of the molecular forms, with a characteristic distribution in various body fluids. Serum IgA is largely monomeric, but in external secretions it exists as S-IgA - a dimer consisting of two IgA molecules bound together by J chain and attached to secretory piece (SC). Both in serum and secretions IgA occurs in two isotypic forms, IgA1 and IgA2. IgA2 exists as two known allotypes, namely IgA2m(1) and IgA2m(2), with a form IgA2(n) possibly representing a third allotype. The major difference between the IgA subclasses is an absence of 13-aminoacid segment in the hinge region of IgA2 that is found in IgA1 molecules. This truncated hinge region in IgA2 molecules renders them resistant to at least two families of IgA1-specific bacterial proteases, which presumably is advantageous to IgA2 antibody function at mucosal surfaces. Further and profound structural difference between the i?1 and ?2 chains concerns the distribution and composition of the oligosaccharide side chains. The IgA1 contains two N-linked glycosylation sites (Asn263 in the CH2 domain and Asn459 in the tail piece) as well as nine potential O-linked glycosylation sites in the hinge region. All three IgA2 variants lack these O-linked sugars, but they have two extra N-linked glycosylation sites (Asn166 in the CH1 and Asn337 in the CH2). The IgA2m(2) and IgA2(n) allotypes have a fifth potential N-linked side in the CH1 (Asn211) domain. The variations in the glycosylation structure of the different form of IgA play a significant role in determining antibodies conformation and assembly, receptors (TCR, ASGP-R) binding and t1/2. Here we review current knowledge concerning the relationship of the structure of human IgA1 to the IgA2 isotype, the polymeric IgA and secretory IgA structures, and IgA function.