A Broad Survey and Functional Analysis of Immunoglobulin Loci Variation in Rhesus Macaques

Area of Science:

• Immunology
• Genomics
• Primate Research

Background:

• Rhesus macaques (RMs) are essential models for human disease research and pre-clinical vaccine studies, especially for understanding antibody responses.
• Robust genetic resources for immunoglobulin (IG) loci are critical for these studies, but their complexity poses challenges.
• Characterizing IG loci accurately is vital for advancing immunogenomics and translational research.

Purpose of the Study:

• To develop novel methodologies for comprehensive characterization of IG loci in Rhesus macaques.
• To generate the largest integrated antibody repertoire and long-read genomic sequencing dataset in RMs to date.
• To create a publicly accessible resource for RM immunogenomics and vaccine discovery.

Main Methods:

• Employed novel experimental and computational approaches for integrated antibody repertoire and long-read genomic sequencing.
• Sequenced 106 Indian origin Rhesus macaques to generate a comprehensive dataset.
• Curated immunoglobulin (IG) heavy and light chain variable (V), diversity (D), and joining (J) alleles, along with associated sequences.

Main Results:

• Generated the largest collection of integrated antibody repertoire and long-read genomic sequencing data in RMs.
• Curated 1474 novel IG alleles, expanding existing allele sets by 60% and revealing significant genetic diversity.
• Established a comprehensive, publicly available resource (https://vdjbase.org/reference_book/Rhesus_Macaque) for RM immunogenomics.

Conclusions:

• The developed resource provides a foundational dataset for advancing Rhesus macaque immunogenomics.
• This work significantly enhances the genetic resources available for RM-based vaccine research and translational studies.
• The findings underscore the vast diversity within RM immunoglobulin loci, crucial for understanding immune responses.