Rhesus macaque MHC class I molecules show differential subcellular localizations

Area of Science:

• Immunogenetics
• Molecular Biology
• Primate Immunology

Background:

• The major histocompatibility complex (MHC) class I gene family in rhesus macaques exhibits significant gene duplications, with expanded Mamu-A and Mamu-B genes.
• While some Mamu genes influence infectious disease outcomes, the functional significance of Mamu-A and Mamu-B gene duplications and their protein expression patterns remain largely unexplored.

Purpose of the Study:

• To investigate the subcellular localization of AcGFP-tagged Mamu-A and Mamu-B molecules in rhesus macaques.
• To understand the functional implications of differential expression patterns of Mamu class I genes.

Main Methods:

• Subcellular localization analysis of AcGFP-tagged Mamu-A and Mamu-B molecules.
• Correlation of expression patterns with specific Mamu gene alleles and their domains.

Main Results:

• Mamu-A and specific Mamu-B alleles (e.g., Mamu-B*01704) demonstrated strong cell surface and low intracellular expression.
• Other Mamu-A and Mamu-B alleles (e.g., Mamu-A4*1403, Mamu-B*01202) exhibited weak cell surface and strong intracellular expression.
• Differential expression was linked to the alpha1 and alpha2 domains, suggesting impaired peptide binding retains molecules intracellularly.

Conclusions:

• Duplicated Mamu class I genes display diverse subcellular localization patterns.
• Varied expression suggests distinct functional roles for Mamu-A and Mamu-B genes in rhesus macaques.
• Failure in peptide binding may explain the intracellular retention of certain Mamu class I molecules.