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Characterization of Mauritian Cynomolgus Macaque FcγR Alleles Using Long-Read Sequencing.

Amelia K Haj1, Jaren M Arbanas2, Aaron P Yamniuk2

  • 1Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705.

Journal of Immunology (Baltimore, Md. : 1950)
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Fc gamma receptors (FcγRs) are key immune proteins. Mauritian cynomolgus macaques (MCMs) show limited FcγR diversity, suggesting reproducibility for antibody therapy studies.

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Area of Science:

  • Immunology
  • Genetics
  • Primate Models

Background:

  • Fc gamma receptors (FcγRs) are crucial immune proteins involved in antibody-mediated immune responses.
  • Genetic variations in FcγRs are linked to autoimmune diseases and other conditions.
  • Mauritian cynomolgus macaques (MCMs) are valuable models for human diseases due to their limited genetic diversity.

Purpose of the Study:

  • To characterize the diversity of Fc gamma receptor (FcγR) genes in Mauritian cynomolgus macaques (MCMs).
  • To develop and utilize a high-throughput genotyping assay for FcγR alleles and haplotypes in MCMs.
  • To assess the impact of FcγR allele variation on antibody-binding affinities.

Main Methods:

  • PacBio long-read sequencing was employed to identify novel FcγR alleles in 48 MCMs.
  • A high-throughput FcγR genotyping assay was developed and applied to over 500 MCMs.
  • Surface plasmon resonance was used to evaluate antibody-binding affinities of different FcγR alleles.

Main Results:

  • Three alleles for FcγR1A, seven each for FcγR2A and FcγR2B, and four for FcγR3A were identified.
  • These alleles segregated into eight distinct FcγR haplotypes within the MCM population.
  • Minimal differences in antibody-binding affinities were observed across the identified FcγR alleles.

Conclusions:

  • MCMs exhibit limited FcγR diversity compared to humans.
  • This restricted diversity may lead to highly reproducible results in monoclonal antibody therapy and toxicity studies.
  • While not fully mirroring human FcγR diversity, MCMs offer a valuable model for specific immunological research.