TY - JOUR
T1 - Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait
AU - Venkataraman, Thiagarajan
AU - Valencia, Cristian
AU - Mangino, Massimo
AU - Morgenlander, William
AU - Clipman, Steven J.
AU - Liechti, Thomas
AU - Valencia, Ana
AU - Christofidou, Paraskevi
AU - Spector, Tim
AU - Roederer, Mario
AU - Duggal, Priya
AU - Larman, H. Benjamin
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - 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.
AB - 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.
KW - Epstein-Barr virus
KW - VirScan
KW - humoral immunity
KW - immunogenetics
KW - viral antibody epitope selection
UR - http://www.scopus.com/inward/record.url?scp=85122287929&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2021.12.004
DO - 10.1016/j.immuni.2021.12.004
M3 - Artículo en revista científica indexada
C2 - 35021055
AN - SCOPUS:85122287929
SN - 1074-7613
VL - 55
SP - 174-184.e5
JO - Immunity
JF - Immunity
IS - 1
ER -
