Increased glycosylation complexity in the singular marsupial IgG subclass 2063

Abstract Description IgG is a uniquely mammalian isotype and the most abundant serum antibody in mammals. It mediates a broad variety of effector functions and can have multiple subclasses that have evolved distinct characteristics in many placental mammals (e.g. humans and mice). There is also variation in the number of IgG subclasses among placental species. Marsupials are a lineage of therian mammals that last shared a common ancestor with placental mammals at least 160 million years ago. We have found that marsupials (e.g. kangaroos and opossums) uniformly have a single IgG subclass. This uniformity is distinctly marsupial as the third lineage of mammals, monotremes (e.g. platypus), also have multiple IgG subclasses. Given the role that glycans found on IgGs in humans and mice impact their effector functions, such as binding to Fc receptors, inflammation, and antibody clearance, we investigated glycosylation in the singular serum IgG from a model marsupial, the laboratory opossum Monodelphis domestica. The single opossum IgG has two distinct glycosylation sites, the most N-terminal of which is in the CH2 domain and highly conserved across all IgG subclasses. The second site, also in CH2, is marsupial specific and has more complex glycans that are distinct from the conserved site. Despite marsupials having only one IgG subclass, there may be compensation via an increased number of glycosylation sites and increased complexity found at those sites. Funding Sources Supported by NSF award IOS-2103367 and NIH R24GM137782. Topic Categories Veterinary and Comparative Immunology (VET)