title: Cynomolgus and pigtail macaque IgG subclasses: characterization of IGHG genes and computational analysis of IgG/Fc receptor binding affinity.
abstract: Macaques are the most widely used experimental nonhuman primate (NHP) species. Rhesus (Macaca mulatta, Macmul), cynomolgus (Macaca fascicularis, Macfas), and pigtail (Macaca nemestrina, Macnem) macaques continue to be popular models for vaccine and infectious diseases research, especially HIV infection and AIDS, and for the development of antibody-based therapeutic strategies. Increased understanding of the immune system of these species is necessary for their optimal use as models of human infections and intervention. In the past few years, the antibody/Fc receptor system has been characterized in a stepwise manner in these species. We have continued this characterization by identifying the four IG heavy gamma (IGHG) genes of Macfas and Macnem in this study. Our results show that these genes share a high degree of similarity with those from other NHP species, while presenting consistent differences when compared to human IGHG genes. Furthermore, comparison of Macfas IGHG genes with those described in other studies suggests the existence of polymorphism. Using sequence- and structure-based computational tools, we performed in silico analysis on multiple polymorphic Macfas IgG and their interactions with human IgG Fc receptors (FcγR), thus predicting that Macfas IGHG polymorphisms influence IgG protein stability and/or binding affinity towards FcγR. The presence of macaque IGHG polymorphisms and macaque/human amino acid changes at locations potentially involved in antibody functional properties indicate the need for cautious design and data interpretation of studies in these models, possibly requiring the characterization of antibody/Fc receptor interactions at the individual level.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
authors.forename: Doan C
authors.initials: DC
authors.lastname: Nguyen
authors.forename: Rashesh
authors.initials: R
authors.lastname: Sanghvi
authors.forename: Franco
authors.initials: F
authors.lastname: Scinicariello
authors.forename: Joanna
authors.initials: J
authors.lastname: Pulit-Penaloza
authors.forename: Nicole
authors.initials: N
authors.lastname: Hill
authors.forename: Roberta
authors.initials: R
authors.lastname: Attanasio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D001666:Binding Sites, Antibody; D003198:Computer Simulation; D006801:Humans; D007129:Immunoglobulin Gm Allotypes / Q000235:genetics*; D008252:Macaca fascicularis / Q000235:genetics* / Q000276:immunology; D008254:Macaca nemestrina / Q000235:genetics* / Q000276:immunology; D018448:Models, Immunological; D008969:Molecular Sequence Data; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D007129:Immunoglobulin Gm Allotypes; D017452:Receptors, IgG