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 c hain is encoded by the alpha gene on chromosome 14. Previous studies h ave indicated the presence of two alpha genes, alpha 1 and alpha 2, wi th 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 deter mination of a novel human alpha gene. Nucleotide sequence comparison w ith the published ar sequences suggests that the gene arose as a conse quence of recombination or gene conversion between the two alpha 2 all eles. We have expressed the gene as a chimeric protein in myeloma cell s indicating that it encodes a functional protein. The novel IgA resem bles 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 populatio ns, multiple alleles of alpha may be present providing IgAs of differe nt structures.