Acute infectious mononucleosis generates persistent, functional EBNA-1 antibodies with high cross-reactivity to alpha-crystalline beta

Author:

Ganta, Krishna Kumar

McManus, Margaret

Blanc, Ross

Wang, Qixin

Jung, Wonyeong

Brody, Robin

Carrington,Mary

Paris, Robert

Chandramouli, Sumana

McNamara, Ryan P

Luzuriaga, Katherine
Author Address

Molecular Medicine, UMass Chan Medical School, Worcester, MA 01605, USA., Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA., Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20814, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21701, USA., Moderna Therapeutics, Cambridge, MA 02142, USA., Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: rmcnamara@hsph.harvard.edu., Molecular Medicine, UMass Chan Medical School, Worcester, MA 01605, USA. Electronic address: katherine.luzuriaga@umassmed.edu.,

Abstract:

We investigate the magnitude, specificity, and functional properties of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1)-specific antibodies in young adults over the course of primary infection. EBNA-1-specific binding antibodies, as well as antibodies capable of antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent complement deposition (ADCD), are detected. These antibodies primarily target a region of EBNA-1 known to elicit cross-reactive antibodies to several self-peptides. Higher EBNA-1 binding and ADCD antibodies are observed in individuals with at least one HLA-DRB1*15:01 allele. Alpha-crystallin beta (CRYAB) binding and complement-fixing antibodies are detected at 6 months and 1 year following infectious mononucleosis, and CRYAB antibodies are resistant to denaturation, consistent with an affinity-matured response. Blocking experiments show that CRYAB antibodies are cross-reactive with EBNA-1. Altogether, high levels of functional EBNA-1 antibodies are generated in primary EBV infection, some of which are cross-reactive with CRYAB. Further investigation is warranted to determine whether these responses contribute to autoimmunity. Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

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