Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait.

Human immune responses to viral infections are highly variable, but the genetic factors that contribute to this variability are not well characterized. We used VirScan, a high-throughput epitope scanning technology, to analyze pan-viral antibody reactivity profiles of twins and SNP-genotyped individuals. Using these data, we determined the heritability and genomic loci associated with antibody epitope selection, response breadth, and control of Epstein-Barr virus (EBV) viral load. 107 EBV peptide reactivities were heritable and at least two Epstein-Barr nuclear antigen 2 (EBNA-2) reactivities were associated with variants in the MHC class II locus. We identified an EBV serosignature that predicted viral load in peripheral blood mononuclear cells and was associated with variants in the MHC class I locus. Our study illustrates the utility of epitope profiling to investigate the genetics of pathogen immunity, reports heritable features of the antibody response to viruses, and identifies specific HLA loci important for EBV epitope selection. [Display omitted] • Performed pan-viral antibody profiling on a cohort of twins and genotyped individuals • Epitope selection and response breadth are heritable traits across several viral genera • EBV epitope-specific reactivities are associated with the MHC class II locus via GWAS • A signature predictive of EBV copies in PBMCs is associated with the MHC class I locus The genes influencing antiviral antibody responses are not well characterized. Venkataraman et al. performed pan-viral antibody profiling on twins and genotyped individuals using VirScan. They found that epitope selection and response breadth are heritable across several genera and identified variants in the MHC class II and class I loci that control EBV antibody epitope selection and viral load control, respectively. [ABSTRACT FROM AUTHOR]