Porcine IgG: structure, genetics, and evolution.

Eleven genomic porcine Cgamma gene sequences are described that represent six putative subclasses that appear to have originated by gene duplication and exon shuffle. The genes previously described as encoding porcine IgG1 and IgG3 were shown to be the IgG1(a) and IgG1(b) allelic variants of the IGHG1 gene, IgG2a and IgG2b are allelic variants of the IGHG2 gene, while "new" IgG3 is monomorphic, has an extended hinge, is structurally unique, and appears to encode the most evolutionarily conserved porcine IgG. IgG5(b) differs most from its putative allele, and its C(H)1 domain shares sequence homology with the C(H)1 of IgG3. Four animals were identified that lacked either IgG4 or IgG6. Alternative splice variants were also recovered, some lacking the C(H)1 domain and potentially encoding heavy chain only antibodies. Potentially, swine can transcribe >20 different Cgamma chains. A comparison of mammalian Cgamma gene sequences revealed that IgG diversified into subclasses after speciation. Thus, the effector functions for the IgG subclasses of each species should not be extrapolated from "same name subclasses" in other species. Sequence analysis identified motifs likely to interact with Fcgamma receptors, FcRn, protein A, protein G, and C1q. These revealed IgG3 to be most likely to activate complement and bind FcgammaRs. All except IgG5(a) and IgG6(a) should bind to FcgammaRs, while all except IgG6(a) and the putative IgG5 subclass proteins should bind well to porcine FcRn, protein A, and protein G.