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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Allelic diversity within the high frequency Mamu-A2*05/Mane-A2*05 (Mane-A*06)/Mafa-A2*05 family of macaque MHC-A loci
J Wu1, S Bassinger, G D Montoya
1Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Abstract:
Macaque species serve as important animal models of human infection and immunity. To more fully scrutinize their potential in both the analysis of disease pathogenesis and vaccine development, it is necessary to characterize the major histocompatibility complex (MHC) class I loci of Macaca mulatta (Mamu), Macaca nemestrina (Mane), and Macaca fascicularis (Mafa) at the genomic level. The oligomorphic Mamu-A2*05/Mane-A2*05 (previously known as Mane-A*06) family of macaque MHC-A alleles has recently been shown to be present at high frequency in both Indian rhesus and pig-tailed macaque populations. Using a locus-specific amplification and direct DNA typing methodology, we have additionally found that the locus encoding this family is very prevalent (75%) among a sampling of 182 Chinese rhesus macaques and has a high prevalence (80%) within a larger, independent cohort of 309 pig-tailed macaques. Interestingly, among the Chinese rhesus macaques, only six alleles previously identified in Indian-origin animals were observed, while three recently identified in Chinese-origin animals and 25 new alleles were characterized. Among the pig-tailed macaques, we observed 1 previously known (Mane-A*06) and 19 new alleles. Examination of the orthologous locus in a preliminary sampling of 30 cynomolgus macaques showed an even higher presence (87%) of Mafa-A2*05 family alleles, with 5 previously identified and 15 new alleles characterized. The continued discovery of novel alleles and thus further diversity within the Mamu-A2*05/Mane-A2*05/Mafa-A2*05 family indicates that this MHC-A locus, although highly conserved across the three species of macaques, has remained a dynamic entity during evolution.
Insights
Macaque major histocompatibility complex (MHC) class I loci are crucial for understanding human disease and developing vaccines. This study characterized MHC-A alleles in Chinese rhesus, pig-tailed, and cynomolgus macaques, revealing significant diversity and novel alleles.
Area of Science:
- Immunogenetics
- Primate genomics
- Comparative immunology
Background:
- Macaque species are vital animal models for human infection and immunity research.
- Genomic characterization of major histocompatibility complex (MHC) class I loci in macaques is essential for disease pathogenesis and vaccine development.
- The Mamu-A2*05/Mane-A2*05 (Mane-A*06) MHC-A allele family is prevalent in Indian rhesus and pig-tailed macaques.
Purpose of the Study:
- To characterize the genomic-level major histocompatibility complex (MHC) class I loci in Macaca mulatta (Mamu), Macaca nemestrina (Mane), and Macaca fascicularis (Mafa).
- To investigate the prevalence and diversity of the Mamu-A2*05/Mane-A2*05/Mafa-A2*05 allele family across different macaque populations.
Main Methods:
- Locus-specific amplification and direct DNA typing methodology were employed.
- Analysis included Chinese rhesus macaques (n=182), pig-tailed macaques (n=309), and cynomolgus macaques (n=30).
- Allele identification and characterization were performed for the MHC-A locus.
Main Results:
- The Mamu-A2*05/Mane-A2*05/Mafa-A2*05 family locus was highly prevalent (75% in Chinese rhesus, 80% in pig-tailed, 87% in cynomolgus macaques).
- Significant novel allele discovery occurred: 25 new alleles in Chinese rhesus, 19 in pig-tailed, and 15 in cynomolgus macaques.
- Despite high conservation across species, the MHC-A locus demonstrated ongoing evolutionary dynamism with substantial genetic diversity.
Conclusions:
- The Mamu-A2*05/Mane-A2*05/Mafa-A2*05 MHC-A locus is a conserved yet dynamic entity across macaque species.
- The high prevalence and extensive novel allele discovery underscore the importance of this locus for macaque immunogenetics.
- Further characterization of macaque MHC diversity is critical for their utility as models in infectious disease and immunology studies.
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