Abstract
Nonhuman primates are important animal models for the study of the maternal immune response to implantation within the decidua. The objective of this study was to define the placental expression of major histocompatibility complex (MHC) class I molecules in the cynomolgus (Macaca fascicularis) and vervet (African green) (Chlorocebus aethiops) monkeys. Early pregnancy (d36-42) cynomolgus and vervet placentas were obtained by fetectomy and prepared for histological evaluation. A pan-MHC class I monoclonal antibody demonstrated MHC class I expression in both vervet and cynomolgus placental trophoblasts, with particularly high expression in the villous syncytium, as previously shown in the rhesus and baboon. Placental cytotrophoblasts were isolated by enzymatic dispersion and gradient centrifugation and cultured, and multicolor flow cytometry was used to phenotype cell populations. Culture of isolated villous cytotrophoblasts demonstrated that MHC class I expression was linked to syncytiotrophoblast differentiation. A monoclonal antibody against Mamu-AG, the nonclassical MHC class I homolog of HLA-G in the rhesus monkey, demonstrated intense immunostaining and cell surface expression in cynomolgus placental trophoblasts; however, staining with vervet placenta and cells was low and inconsistent. Reverse transcriptase polymerase chain reaction was used to clone MHC class I molecules expressed in cynomolgus and vervet placentas. While Mafa-AG messenger RNA (mRNA) was readily detectable in cynomolgus placental RNA and was >99% identical at the amino acid level with Mamu-AG, 7/8 Chae-AG complementary DNAs had an unusual 16 amino acid repeat in the α1 domain, and all clones had an unexpected absence of the early stop codon at the 3′-end of the mRNA diagnostic for rhesus, cynomolgus, and baboon AG mRNAs, as well as HLA-G. We conclude that while the vervet monkey has retained the placental expression of a primate-specific nonclassical MHC class I locus, diversity is also revealed in this locus expressed at the maternal–fetal interface, thought to participate in placental regulation of the maternal immune response to embryo implantation and pregnancy.
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Acknowledgments
We thank the Veterinary, CPI, and the Assay Service Units for assistance in developing methods for monitoring vervet monkey reproductive cycles, producing timed matings and monitoring serum hormones. The veterinary staff of the Wisconsin National Primate Research Center provided excellent surgical assistance, and we thank Judith Peterson for assistance in preparation of this manuscript. Dr. David O’Connor and the WNPRC Immunogenetics Core provided advice on primer design and MHC class I nomenclature procedures. This research was supported by NIH grants RR14040, HD37120, AI076734, and HD34215 to T.G.G., GM43940 to A.L.H., and P51 RR000167 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH.
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Gennadiy I. Bondarenko and Svetlana V. Dambaeva contributed equally to this work.
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Bondarenko, G.I., Dambaeva, S.V., Grendell, R.L. et al. Characterization of cynomolgus and vervet monkey placental MHC class I expression: diversity of the nonhuman primate AG locus. Immunogenetics 61, 431–442 (2009). https://doi.org/10.1007/s00251-009-0376-9
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DOI: https://doi.org/10.1007/s00251-009-0376-9