Alleles and isoforms of human membrane-bound IgA1.
In humans, IgA exists as two subclasses, IgA1 and IgA2, which contain distinct alpha1 and alpha2 heavy chains, respectively. Both subclasses also have membrane-bound forms (mIgA1 and mIgA2) containing the corresponding malpha1 and malpha2 heavy chains, which differ from alpha1 and alpha2 by an additional "membrane-anchor" peptide segment extending from the CH3 domain of alpha1 and alpha2. The membrane-anchor segment has three parts: an extracellular, a transmembrane, and an intracellular segment. The heavy chain malpha1 exists in short and long isoforms, referred to as malpha1S and malpha1L, 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 malpha1 and malpha2 from 30 individuals residing in Taiwan, we have found that, in addition to the known malpha1 allele, referred to as malpha1(456S), malpha1 also has a previously unknown allele, referred to as malpha1(456C) (GenBank accession no. EU431191). This newly identified allele is present in the donor population at a similar proportion to malpha1(456S), and appears to exist only as the long isoform, i.e. malpha1L, rather than the short isoform, malpha1S. Furthermore, we confirmed that malpha2 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.
Hung
Alfur Fu-Hsin
AF
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan.
Chen
Jiun-Bo
JB
Chang
Tse Wen
TW
D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D007070:Immunoglobulin A; D008565:Membrane Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger