Characterization of anti-EBNA-1 antibodies and exploration of their molecular mimicry potential in an EBV-infected Sjo<spacing diaeresis>gren's syndrome patient

被引：0

作者：

Hsieh, Shang-Ju ^{[1
,4
]}

Tsai, Tsung-Hsun ^{[2
,4
]}

Lin, Jiun-Han ^{[3
,4
]}

Lin, Tsai-Yu ^{[4
,5
]}

Chang, Fu-Lin ^{[4
,6
]}

Chiang, Chen-Wei ^{[4
,7
]}

Li, Pei Jhen ^{[4
,6
]}

Zheng, Jia Huei ^{[4
,8
]}

Tsai, Keng-Chang ^{[4
,9
,10
]}

Hung, Ching-Sheng ^{[11
]}

Lee, Yu-Ching ^{[1
,4
,5
,6
,10
]}

机构：

[1] Far Eastern Mem Hosp, Dept Surg, Div Urol, New Taipei City, Taiwan

[2] Kaohsiung Armed Forces Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan

[3] MOEA Minist Econ Affairs, Dept Ind Technol, Taipei, Taiwan

[4] Food Ind & Res Dev Inst, Hsinchu, Taiwan

[5] Taipei Med Univ, Coll Med Sci & Technol, Ph D Program Canc Mol Biol & Drug Discovery, Taipei, Taiwan

[6] Taipei Med Univ, TMU Res Ctr Canc Translat Med, Taipei, Taiwan

[7] Taipei Med Univ, Coll Pharm, Ph D Program Drug Discovery & Dev Ind, Taipei, Taiwan

[8] Buddhist Tzu Chi Med Fdn, Hualien Tzu Chi Hosp, Dept Anesthesiol, Hualien, Taiwan

[9] Minist Hlth & Welf, Natl Res Inst Chinese Med, Taipei, Taiwan

[10] Taipei Med Univ, Coll Med Sci & Technol, Ph D Program Med Biotechnol, Taipei, Taiwan

[11] Taipei Med Univ, Wan Fang Hosp, Dept Lab Med, Taipei, Taiwan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2024年 / 735卷

关键词：

EPSTEIN-BARR-VIRUS; SJOGRENS-SYNDROME; POSSIBLE INVOLVEMENT; DISEASE;

D O I：

10.1016/j.bbrc.2024.150839

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

There is a potential link between autoimmune diseases and Epstein-Barr virus (EBV) infections, with EBV playing a substantial role in the onset of Sjo<spacing diaeresis>gren's syndrome (SjS). Some EBV proteins could mimic host self-antigens post-infection, leading to molecular mimicry. This similarity may cause the immune system to attack its tissues mistakenly. Among the various proteins associated with EBV, nuclear antigen 1 (EBNA-1) is essential for the latent replication of infected cells and is prevalent in all EBV-related diseases. In the study, single-chain variable fragment (scFv) antibodies targeting EBNA-1 were isolated using phage display technology from a primary SjS patient who also had a chronic active EBV infection. The specific clones were enriched after panning, and the binding activity of selected scFvs targeting EBNA-1 was confirmed. Sequence analysis indicated that the scFvs exhibiting positive signals could be grouped into five clones, all of which used homologous heavy chain V regions derived from germline Vh4-39, and two types of light chain V regions stemming from germline V lambda 1-44 and V lambda 3-15. These scFvs were found to exhibit a high degree of somatic mutations, likely indicative of antigen selection. Of the scFvs, P1-3 demonstrated the strongest binding affinity to EBNA-1, exhibiting a determined value of 7.3 x 10_8 M, and showed cross-reactivity to the SjS associated La/SSB self-antigen. The experimental results combined with AlphaFold 3 predictions revealed a potential epitope for scFv P1-3 binding to EBNA-1. Additionally, scFv P1-3 could also cross-bind to the modeled structure of La/SSB. We inferred a possible structural correlation between EBNA-1 and La/SSB involving an X2AX6PG epitope motif. This research contributes to our understanding of the structural basis of the interactions between antibodies and EBNA-1, shedding light on the VH and VL gene usage of anti-EBNA-1 antibodies in EBV-infected SjS patients and the potential origins of autoantibodies.

引用

页数：9