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Characterization of pig-tailed macaque classical MHC class I genes: implications for MHC evolution and antigen
Bernard A P Lafont1, Alicia Buckler-White, Ron Plishka
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
MHC-dependent CD8(+) T cell responses have been associated with control of viral replication and slower disease progression during lentiviral infections. Pig-tailed macaques (Macaca nemestrina) and rhesus monkeys (Macaca mulatta), two nonhuman primate species commonly used to model HIV infection, can exhibit distinct clinical courses after infection with different primate lentiviruses. As an initial step in assessing the role of MHC class I restricted immune responses to these infections, we have cloned and characterized classical MHC class I genes of pig-tailed macaques and have identified 19 MHC class I alleles (Mane) orthologous to rhesus macaque MHC-A, -B, and -I genes. Both Mane-A and Mane-B loci were found to be duplicated, and no MHC-C locus was detected. Pig-tailed and rhesus macaque MHC-A alleles form two groups, as defined by 14 polymorphisms affecting mainly their B peptide-binding pockets. Furthermore, an analysis of multiple pig-tailed monkeys revealed the existence of three MHC-A haplotypes. The distribution of these haplotypes in various Old World monkeys provides new insights about MHC-A evolution in nonhuman primates. An examination of B and F peptide-binding pockets in rhesus and pig-tailed macaques suggests that their MHC-B molecules present few common peptides to their respective CTLs.
Insights
Researchers characterized pig-tailed macaque MHC class I genes, identifying 19 alleles and duplicated Mane-A and Mane-B loci. This work advances understanding of immune responses in nonhuman primate models of lentiviral infections.
Area of Science:
- Immunogenetics
- Primate immunology
- Molecular evolution
Background:
- MHC class I-restricted CD8(+) T cell responses are crucial for controlling lentiviral infections.
- Nonhuman primate models, like pig-tailed macaques (Macaca nemestrina) and rhesus monkeys (Macaca mulatta), are vital for studying HIV infection.
Purpose of the Study:
- To clone and characterize classical MHC class I genes in pig-tailed macaques.
- To identify MHC class I alleles and loci in pig-tailed macaques.
- To compare MHC class I structures between pig-tailed and rhesus macaques.
Main Methods:
- Cloning and characterization of pig-tailed macaque MHC class I genes.
- Identification of MHC class I alleles orthologous to rhesus macaque genes.
- Analysis of polymorphisms in peptide-binding pockets.
- Haplotype analysis of MHC-A genes.
Main Results:
- 19 MHC class I alleles (Mane) were identified in pig-tailed macaques, orthologous to rhesus macaque MHC-A, -B, and -I.
- Both Mane-A and Mane-B loci were found to be duplicated; no MHC-C locus was detected.
- MHC-A alleles grouped into two clusters based on polymorphisms, and three MHC-A haplotypes were identified in pig-tailed macaques.
- MHC-B molecules in both species appear to present limited common peptides to CTLs.
Conclusions:
- The characterization of pig-tailed macaque MHC class I genes provides essential data for studying lentiviral infections in this model.
- The duplicated Mane-A and Mane-B loci and identified haplotypes offer insights into MHC-A evolution in primates.
- Comparative analysis of MHC-B peptide-binding pockets suggests species-specific CTL responses.