NKp44 expression, phylogenesis and function in non-human primate NK cells.

Area of Science:

• Immunology
• Evolutionary Biology
• Primate Genetics

Background:

• The natural cytotoxicity receptor (NCR) NKp44 plays a crucial role in immune responses but its characterization beyond Homo sapiens has been limited.
• Understanding NKp44 evolution offers insights into primate immune system divergence.

Purpose of the Study:

• To characterize the NKp44 triggering receptor in Pan troglodytes (chimpanzees) and Macaca fascicularis (macaques).
• To investigate the genomic locus and transcription of NKp44 in these species.
• To compare NKp44 expression and function with Homo sapiens.

Main Methods:

• Phenotypic, molecular, and functional characterization of NKp44 on primate NK cells.
• Analysis of NKp44 genomic organization and transcription patterns.
• In vitro functional assays of activated NK cells.

Main Results:

• NKp44 is expressed on activated chimpanzee NK cells, with higher basal transcription but lower differential increase upon activation compared to humans.
• Chimpanzee NKp44 shows lower gene expression but similar surface expression post-activation compared to humans, suggesting post-transcriptional regulation.
• Macaca fascicularis exhibits very low NKp44 transcription, out-of-frame transcripts, and no surface expression, indicating recent emergence of NKp44 organization during speciation.

Conclusions:

• NKp44 evolution shows distinct transcriptional and post-transcriptional tuning differences between humans and chimpanzees.
• NKp44 appears to be a recently emerged NCR, gaining functional relevance in primates closest to Homo sapiens.
• Comparative analysis highlights the dynamic evolution of immune receptors during primate speciation.