Antiviral Antibody Epitope Selection is a Heritable Trait

Venkataraman, T.; Valencia, C.; Mangino, M.; Morgenlander, W.; Clipman, S. J.; Liechti, T.; Valencia, A.; Christofidou, P.; Spector, T. D.; Roederer, M.; Duggal, P.; Larman, H. B.

doi:10.1101/2021.03.25.436790

bioRxiv · 10.1101/2021.03.25.436790

Antiviral Antibody Epitope Selection is a Heritable Trait

Venkataraman, T.·Valencia, C.·Mangino, M.·Morgenlander, W.·Clipman, S. J.·Liechti, T.·Valencia, A.·Christofidou, P.·Spector, T. D.·Roederer, M.·Duggal, P.·Larman, H. B.

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Abstract

There is enormous variability in human immune responses to viral infections. However, the genetic factors that underlie this variability are not well characterized. We used VirScan, a high-throughput viral epitope scanning technology, to analyze the antibody binding specificities of twins and SNP-genotyped individuals. These data were used to estimate the heritability and identify genomic loci associated with antibody epitope selection, response breadth, and the control of Epstein-Barr Virus (EBV) viral load. We identified 4 epitopes of EBV that were heritably targeted, and at least two EBNA-2 binding specificities that were associated with variants in the MHC class-II locus. We identified an EBV serosignature that predicted viral load in white blood cells and was associated with genetic variants in the MHC class-I locus. Our study provides a new framework for identifying genes important for pathogen immunity, with specific implications for the genetic architecture of EBV humoral responses and the control of viral load. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

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Venkataraman, T., Valencia, C., Mangino, M., Morgenlander, W., Clipman, S. J., Liechti, T., Valencia, A., Christofidou, P., Spector, T. D., Roederer, M., Duggal, P., Larman, H. B.. 2021-03-26. Antiviral Antibody Epitope Selection is a Heritable Trait. https://doi.org/10.1101/2021.03.25.436790

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