Alleles and isoforms of human membrane-bound IgA1

In humans, IgA exists as two subclasses, IgA1 and IgA2, which contain distinct α1 and α2 heavy chains, respectively. Both subclasses also have membrane-bound forms (mIgA1 and mIgA2) containing the corresponding mα1 and mα2 heavy chains, which differ from α1 and α2 by an additional “membrane-anchor” peptide segment extending from the CH3 domain of α1 and α2. The membrane-anchor segment has three parts: an extracellular, a transmembrane, and an intracellular segment. The heavy chain mα1 exists in short and long isoforms, referred to as mα1S and mα1L, with the latter containing extra 6 amino acid residues, GSCSVA, at the N-terminus of the extracellular segment (residues 453–458). By studying the genomic and mRNA sequences of mα1 and mα2 from 30 individuals residing in Taiwan, we have found that, in addition to the known mα1 allele, referred to as mα1(456S), mα1 also has a previously unknown allele, referred to as mα1(456C) (GenBank accession no. EU431191). This newly identified allele is present in the donor population at a similar proportion to mα1(456S), and appears to exist only as the long isoform, i.e. mα1L, rather than the short isoform, mα1S. Furthermore, we confirmed that mα2 exists only as the short isoform. Future studies will examine whether these mIgA1 variations affect the regulation of IgA synthesis and whether mIgA1 can provide an antigenic site for the immunological targeting of IgA-expressing B cells.