Characterization of Mauritian Cynomolgus Macaque Fc{gamma}R Alleles Using Long-Read Sequencing [IMMUNOGENETICS]

The FcRs are immune cell surface proteins that bind IgG and facilitate cytokine production, phagocytosis, and Ab-dependent, cell-mediated cytotoxicity. FcRs play a critical role in immunity; variation in these genes is implicated in autoimmunity and other diseases. Cynomolgus macaques are an excellent animal model for many human diseases, and Mauritian cynomolgus macaques (MCMs) are particularly useful because of their restricted genetic diversity. Previous studies of MCM immune gene diversity have focused on the MHC and killer cell Ig-like receptor. In this study, we characterize FcR diversity in 48 MCMs using PacBio long-read sequencing to identify novel alleles of each of the four expressed MCM FcR genes. We also developed a high-throughput FcR genotyping assay, which we used to determine allele frequencies and identify FcR haplotypes in more than 500 additional MCMs. We found three alleles for FcR1A, seven each for FcR2A and FcR2B, and four for FcR3A; these segregate into eight haplotypes. We also assessed whether different FcR alleles confer different Ab-binding affinities by surface plasmon resonance and found minimal difference in binding affinities across alleles for a panel of wild type and Fc-engineered human IgG. This work suggests that although MCMs may not fully represent the diversity of FcR responses in humans, they may offer highly reproducible results for mAb therapy and toxicity studies.

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