Elucidation of a simple role in the antibody diversity

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21909
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Jikei University School of Medicine
• Principal Investigator: SHIRAISHI KOICHI 東京慈恵会医科大学, 医学部, 准教授 (40426284)
• Co-Investigator(Kenkyū-buntansha): 望月 慎一 北九州市立大学, 国際環境工学部, 准教授 (10520702)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: ポリエチレングリコール / 免疫原性 / 抗体

Outline of Final Research Achievements

Diversity of antibodies is a key function for our defense system. We have found that anti-PEG antibodies (anti-PEG Abs) exhibit very weak interaction to PEG chains. This characteristic of anti-PEG Abs specific to macromolecule PEG chains indicates occurrence of PEG-related interaction to other biomolecules regardless biomolecules’ specificity (especially antibodies’ specificity). Our hypothesis is, firstly, that a PEG chain, as an antigen, comes close to not only PEG-specific antibodies, but also non-PEG specific antibodies. Second, owing to a characteristic of PEG’s widespread specificity, part of interacted antibodies exhibit greater affinity if PEGs have possessed conjugated blocks (lipids, and proteins). We have detected that PEGs interacted to non-PEG specific IgM antibodies, as well as PEG-specific IgM antibodies. This observation have answered why PEG-related antibody responses have been frequently observed in healthy subjects and animal models.

Free Research Field

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Academic Significance and Societal Importance of the Research Achievements

本研究で得られた結果はPEGが抗原として、特に免疫初期応答を担うIgM抗体に対して、PEG特異的抗体、および非PEG特異的抗体に作用し、その結合親和性に大きな差がないことを明らかとした。即ち、PEGのもつ他分子（抗体）へ近づけるという性質がPEGの特異性の幅の広さを示し、PEG特異的抗体産生という現象が現れやすい一つの原因を示唆していると考えられる。PEGのもつ近づけるという性質に加えて、相手となる抗体側に、より強固となる結合を補完する領域が特異的相互作用の場に存在することが重要であることを明らかとした。これは、古典的な抗体と抗原との関係を考える際に新たな視点を与えると考えられる。