Document Type

Article

Publication Date

1-2023

Identifier

DOI: 10.3389/fimmu.2023.1306292; PMCID: PMC10803544

Abstract

Fcγ receptors (FcγRs) are membrane-bound glycoproteins that bind to the fragment crystallizable (Fc) constant regions of IgG antibodies. Interactions between IgG immune complexes and FcγRs can initiate signal transduction that mediates important components of the immune response including activation of immune cells for clearance of opsonized pathogens or infected host cells. In humans, many studies have identified associations between FcγR gene polymorphisms and risk of infection, or progression of disease, suggesting a gene-level impact on FcγR-dependent immune responses. Rhesus macaques are an important translational model for most human health interventions, yet little is known about the breadth of rhesus macaque FcγR genetic diversity. This lack of knowledge prevents evaluation of the impact of FcγR polymorphisms on outcomes of preclinical studies performed in rhesus macaques. In this study we used long-read RNA sequencing to define the genetic diversity of FcγRs in 206 Indian-origin Rhesus macaques, Macaca mulatta. We describe the frequency of single nucleotide polymorphisms, insertions, deletions, frame-shift mutations, and isoforms. We also index the identified diversity using predicted and known rhesus macaque FcγR and Fc-FcγR structures. Future studies that define the functional significance of this genetic diversity will facilitate a better understanding of the correlation between human and macaque FcγR biology that is needed for effective translation of studies with antibody-mediated outcomes performed in rhesus macaques.

Journal Title

Front Immunol

Volume

14

First Page

1306292

Last Page

1306292

MeSH Keywords

Humans; Animals; Macaca mulatta; Receptors, IgG; Sequence Analysis, RNA; Antigen-Antibody Complex; Frameshift Mutation; Immunoglobulin G; Membrane Glycoproteins

Keywords

Fc receptor; FcγR SNPs; FcγR structures; Long-read RNA sequencing; genetic diversity; rhesus macaques

Comments

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Publisher's Link: https://www.frontiersin.org/articles/10.3389/fimmu.2023.1306292/full

Download

Share

COinS