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

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-05-13 DOI:10.1016/j.celrep.2025.115709

Krishna Kumar Ganta, Margaret McManus, Ross Blanc, Qixin Wang, Wonyeong Jung, Robin Brody, Mary Carrington, Robert Paris, Sumana Chandramouli, Ryan P McNamara, Katherine Luzuriaga

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引用次数: 0

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.

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急性传染性单核细胞增多症产生持久的、功能性的EBNA-1抗体，对α结晶β具有高交叉反应性。

我们研究了原发性感染过程中年轻人eb病毒（EBV）核抗原1 （EBNA-1）特异性抗体的大小、特异性和功能特性。检测ebna -1特异性结合抗体，以及能够进行抗体依赖性细胞吞噬（ADCP）和抗体依赖性补体沉积（ADCD）的抗体。这些抗体主要针对已知的EBNA-1区域，该区域可引发针对几种自身肽的交叉反应抗体。在具有至少一个HLA-DRB1∗15:01等位基因的个体中观察到较高的ena -1结合和ADCD抗体。在感染性单核细胞增多症后6个月和1年检测到α -结晶蛋白β (CRYAB)结合抗体和补体固定抗体，CRYAB抗体对变性具有抗性，与亲和成熟反应一致。阻断实验表明，CRYAB抗体与ena -1有交叉反应。总之，在原发性EBV感染中产生高水平的功能性EBNA-1抗体，其中一些抗体与CRYAB交叉反应。需要进一步调查以确定这些反应是否有助于自身免疫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.