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

Thiagarajan Venkataraman, Cristian Valencia, Massimo Mangino, William Morgenlander, Steven J. Clipman, Thomas Liechti, Ana Valencia, Paraskevi Christofidou, Tim Spector, Mario Roederer, Priya Duggal, H. Benjamin Larman

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)174-184.e5
JournalImmunity
Volume55
Issue number1
DOIs
StatePublished - Jan 11 2022

Keywords

  • Epstein-Barr virus
  • VirScan
  • humoral immunity
  • immunogenetics
  • viral antibody epitope selection

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology

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