Porcine IgG: structure, genetics, and evolution

• Published in: Immunogenetics (New York) 2009-03, Vol.61 (3), p.209-230
• Main Authors: Butler, J. E, Wertz, Nancy, Deschacht, Nicholas, Kacskovics, Imre
• Format: Article
• Language: English
• Subjects: Allergology; Amino Acid Sequence; Animals; Antibodies; Base Sequence; Biomedical and Life Sciences; Biomedicine; Cell Biology; Comparative immunology; Evolution; Evolution, Molecular; Fc receptors; Gene Function; Genes; Genetic testing; Genetics; Human Genetics; IgG subclasses; Immunoglobulin G - chemistry; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunology; Molecular Sequence Data; Original Paper; Phylogeny; Proteins; Speciation; Swine - genetics; Swine - immunology
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s00251-008-0336-9

Eleven genomic porcine Cγ 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 IgG1a and IgG1b 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. IgG5b differs most from its putative allele, and its CH1 domain shares sequence homology with the CH1 of IgG3. Four animals were identified that lacked either IgG4 or IgG6. Alternative splice variants were also recovered, some lacking the CH1 domain and potentially encoding heavy chain only antibodies. Potentially, swine can transcribe >20 different Cγ chains. A comparison of mammalian Cγ 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 Fcγ receptors, FcRn, protein A, protein G, and C1q. These revealed IgG3 to be most likely to activate complement and bind FcγRs. All except IgG5a and IgG6a should bind to FcγRs, while all except IgG6a and the putative IgG5 subclass proteins should bind well to porcine FcRn, protein A, and protein G.