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

doi:10.1016/j.immuni.2021.12.004

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 scientific journal › Article in an indexed scientific journal › peer-review

30 Scopus citations

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 language	English
Pages (from-to)	174-184.e5
Journal	Immunity
Volume	55
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2021.12.004
State	Published - 11 Jan 2022

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Types Minciencias

Artículos de investigación con calidad A1 / Q1

Access to Document

10.1016/j.immuni.2021.12.004

Cite this

Venkataraman, T., Valencia, C., Mangino, M., Morgenlander, W., Clipman, S. J., Liechti, T., Valencia, A., Christofidou, P., Spector, T., Roederer, M., Duggal, P., & Larman, H. B. (2022). Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait. Immunity, 55(1), 174-184.e5. https://doi.org/10.1016/j.immuni.2021.12.004

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

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.",

keywords = "Epstein-Barr virus, VirScan, humoral immunity, immunogenetics, viral antibody epitope selection",

author = "Thiagarajan Venkataraman and Cristian Valencia and Massimo Mangino and William Morgenlander and Clipman, \{Steven J.\} and Thomas Liechti and Ana Valencia and Paraskevi Christofidou and Tim Spector and Mario Roederer and Priya Duggal and Larman, \{H. Benjamin\}",

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doi = "10.1016/j.immuni.2021.12.004",

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Venkataraman, T, Valencia, C, Mangino, M, Morgenlander, W, Clipman, SJ, Liechti, T, Valencia, A, Christofidou, P, Spector, T, Roederer, M, Duggal, P & Larman, HB 2022, 'Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait', Immunity, vol. 55, no. 1, pp. 174-184.e5. https://doi.org/10.1016/j.immuni.2021.12.004

Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait. / Venkataraman, Thiagarajan; Valencia, Cristian; Mangino, Massimo et al.
In: Immunity, Vol. 55, No. 1, 11.01.2022, p. 174-184.e5.

Research output: Contribution to scientific journal › Article in an indexed scientific journal › peer-review

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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

PY - 2022/1/11

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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

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KW - humoral immunity

KW - immunogenetics

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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 -

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

Abstract

Bibliographical note

UN SDGs

Keywords

Types Minciencias

Access to Document

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