The Cynomolgus Macaque MHC Polymorphism in Experimental Medicine

Abstract

Among the non-human primates used in experimental medicine, cynomolgus macaques (Macaca fascicularis hereafter referred to as Mafa) are increasingly selected for the ease with which they are maintained and bred in captivity. Macaques belong to Old World monkeys and are phylogenetically much closer to humans than rodents, which are still the most frequently used animal model. Our understanding of the Mafa genome has progressed rapidly in recent years and has greatly benefited from the latest technical advances in molecular genetics. Cynomolgus macaques are widespread in Southeast Asia and numerous studies have shown a distinct genetic differentiation of continental and island populations. The major histocompatibility complex of cynomolgus macaque (Mafa MHC) is organized in the same way as that of human, but it differs from the latter by its high degree of classical class I gene duplication. Human polymorphic MHC regions play a pivotal role in allograft transplantation and have been associated with more than 100 diseases and/or phenotypes. The Mafa MHC polymorphism similarly plays a crucial role in experimental allografts of organs and stem cells. Experimental results show that the Mafa MHC class I and II regions influence the ability to mount an immune response against infectious pathogens and vaccines. MHC also affects cynomolgus macaque reproduction and impacts on numerous biological parameters. This review describes the Mafa MHC polymorphism and the methods currently used to characterize it. We discuss some of the major areas of experimental medicine where an effect induced by MHC polymorphism has been demonstrated.

Avian MHC Evolution in the Era of Genomics: Phase 1.0

“…There is conclusive evidence for classical and non-classical MHC class I (MHC-I) or MHC class IIB (MHC-IIB) in Galliform species such as the chicken, the turkey ( Meleagris gallopavo ), the black grouse ( Tetrao tetrix ), and the golden pheasant ( Chrysolophus pictus) [5,36,44,45,46,47,48,49]. Possessing both classical and non-classical MHC genes appears to be a taxonomically widespread phenomenon because it has been observed in primates, fish, amphibians, and reptiles [50,51,52,53,54]. Classical MHC genes are usually highly expressed, polymorphic, and have a well-established function in presenting antigens to T-cells [55].…”

First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

“…Nonhuman primate models, including macaques, are frequently used for clinical and nonclinical research due to the phylogenetic proximity and anatomic and physiologic similarities of their reproductive organs to humans. The phylogenetic proximity of the immune and reproductive systems allows for the extrapolation of macaque-based organ transplantation and reproductive medicine studies to humans [ 17 ]. However, as the size of a female macaque is approximately 3–4 kg—quite small compared to humans—fine surgical techniques are required.…”

Characterization of 100 extended major histocompatibility complex haplotypes in Indonesian cynomolgus macaques

“…The class II region includes six distinct loci, which are the same in humans and macaques: DRA, DRB, DQA1, DQB1, DPA1, and DPB1 (Shiina et al, 2017). Because macaques are commonly used as models for infectious disease, vaccine, and transplant studies, an emphasis has been placed on characterizing their MHC polymorphisms Shiina and Blancher, 2019).…”

“…Researchers using nonhuman primate (NHP) transplantation models need to control for differences in the MHC genotypes of donor and recipient tissues and often will vary degrees of disparity when testing tolerance therapies (Burwitz et al, 2017;Kean et al, 2012;Shiina and Blancher, 2019). The National Institutes of Health (NIH) has recognized the need for and importance of transplant research conducted in NHP models since many immunomodulatory strategies that promote tolerance in rodent models have failed to translate successfully to humans (Knechtle et al, 2019).…”

“…A number of investigators have used ICM (Ezzelarab et al, 2016;Zhang et al, 2015) as well as cynomolgus macaques from various other geographic origins ( Kato et al, 2017;Matsunami et al, 2019;Shiina and Blancher, 2019) for transplantation studies. For instance, ICM were used in a study to investigate T cell and alloantibody responses with purposely mismatched donor and recipient pairs (Ezzelarab et al, 2016).…”