Divergence of human alpha-chain constant region gene sequences. A novel recombinant alpha 2 gene

IgA is the major Ig synthesized in humans and provides the first line of defense at the mucosal surfaces. The constant region of IgA heavy chain is encoded by the alpha gene on chromosome 14. Previous studies have indicated the presence of two alpha genes, alpha 1 and alpha 2, with alpha 2 existing in two allotypic forms, alpha 2 m(1) and alpha 2 m(2). Here we report the cloning and complete nucleotide sequence determination of a novel human alpha gene. Nucleotide sequence comparison with the published alpha sequences suggests that the gene arose as a consequence of recombination or gene conversion between the two alpha 2 alleles. We have expressed the gene as a chimeric protein in myeloma cells indicating that it encodes a functional protein. The novel IgA resembles IgA2 m(2) in that disulfide bonds link H and L chains. This novel recombinant gene provides insights into the mechanisms of generation of different constant regions and suggests that within human populations, multiple alleles of alpha may be present providing IgAs of different structures.