A novel, nonclassical MHC class I molecule specific to the common chimpanzee

Area of Science:

• Comparative genomics
• Immunogenetics
• Evolutionary biology

Background:

• Human leukocyte antigen (HLA) class I genes have functional orthologues in chimpanzees.
• A novel nonclassical MHC class I gene, Patr-AL, exists in chimpanzees but not humans or other African apes.

Purpose of the Study:

• To characterize the novel chimpanzee Patr-AL gene and its evolutionary relationship to human and other ape MHC class I genes.
• To investigate the expression, polymorphism, and potential function of Patr-AL.

Main Methods:

• Comparative genomic analysis of MHC class I genes in humans and chimpanzees.
• Gene sequencing and population genetics to assess Patr-AL polymorphism.
• Gene expression analysis in peripheral blood mononuclear cells (PBMC) and B cell lines.
• Biochemical characterization of the Patr-AL polypeptide.
• Functional assays using chimpanzee NK cells.

Main Results:

• Patr-AL is similar to orangutan Popy-A, suggesting orthology, and diverged from MHC-A over 20 million years ago.
• Patr-AL exhibits low polymorphism with only three identified allotypes.
• Patr-AL is expressed at low levels in PBMC and B cells, with characteristics similar to classical MHC class I molecules.
• No inhibition of chimpanzee NK cells by Patr-AL was observed.
• Patr-AL is found in 50% of chimpanzee haplotypes and is associated with repetitive elements, similar to a human HLA-A*2901 relic.

Conclusions:

• Patr-AL represents a distinct class I lineage potentially involved in innate immunity in chimpanzees.
• The presence of Patr-AL may confer immune responses in chimpanzees absent in humans.
• Comparative analysis reveals unique evolutionary trajectories of MHC class I genes in primates.