Evolution and characterization of the Fc-mediated response in bats 2331633

Abstract Introduction Bats (order Chiroptera) serve as important reservoirs of known and potentially zoonotic pathogens, driven partially by novel immune adaptations. However, their adaptive immune systems remain largely uncharacterized, and the extent of immune diversity across bat species is unknown; this is a fascinating non-model system to understand the evolution of antiviral immunity. Some bat species fail to generate neutralizing antibodies during viral infection, suggesting the importance of non-neutralizing antibodies and Fc-mediated signaling in the antiviral immune response. Here, I characterize components of the Fc-mediated response, specifically the immunoglobulin heavy chain constant (IGHC) locus, Fc receptors (FcR), and Fc receptor-like proteins (FCRLs) in high-quality bat genomes. Methods High quality Bat1K and publicly available genomes were annotated using the Tool to infer Orthologs from Genome Alignments 2 (TOGA2). Due to the complexity of the IGHC locus, Fc genes were annotated manually in Geneious. Fc, FcR, and FCRL sequences were extracted and screened for N-linked glycosylation sites, immunoreceptor tyrosine-based activation (ITAM) and inhibition (ITIM) motifs. Results Bats contain canonical IGHC genes (IGHM, IGHG, IGHE, IGHA, variably IGHD), and most human FcR. However, IGHC genes vary in copy number, and contain bat-specific glycosylation sites not found in human Fc. There are also taxon-specific losses of FcεR2, the low-affinity IgE receptor. Further, there may be a tradeoff between FcαR and FcαμR; species that have retained FcαR have lost FcαμR, and vice versa. Other analyses are in progress. Conclusion Bats and their immune systems are extremely diverse. Further biochemical, structural, and functional analysis of Fc-FcR interactions and how the Fc-mediated immune response varies across species will contribute to our growing knowledge of bat antiviral immunity, which could inform the development of vaccines and therapeutics to improve human health. Funding Source NSF DBI 2515340 Topic Categories Veterinary and Comparative Immunology (VET)