Elucidation of non-immunogen-related immunological memory

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19901
• 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): 2022-06-30 – 2024-03-31
• Keywords: PEG / 抗体 / 構造変化

Outline of Final Research Achievements

We examined a hypothesis that repeated injections of haptenic PEGs induce suitable structural changes of anti-PEG antibodies (anti-PEG Abs), in other words, anti-PEG receptors, therefore, anti-PEG receptors become more sensitive to PEGs than the naive state of anti-PEG receptors. Anti-PEG Abs specifically exhibited interactions to PEGs, and the interaction was enhanced PEG’s concentration- and molecular weight-dependent manner. As a result, we observed that low affinity PEGs (MW = 12,000), which is immediately dissociated from anti-PEG Abs, was stayed on anti-PEG Abs by means of GPC and ELISA. This suggests that suitable conformational changes of anti-PEG Abs for PEGs has induced. Furthermore, we observed that high doses of PEG injection induced much sensitive anti-PEG Ab responses, which was confirmed by following immunogenic PEG injections. In sum, non-immunogenic, but haptenic PEGs possibly induce suitable conformational changes of anti-PEG Abs for PEG.

Free Research Field

バイオマテリアルサイエンス

Academic Significance and Societal Importance of the Research Achievements

抗体構造は平衡状態にあり、最適な構造の際に抗原と結合するconformational selectionと、抗原と抗体が結合した後に構造変化が誘導されるInduced-fitがあるとされる。本研究は、濃厚PEG溶液という外的要因に基づく構造変化（conformational selection）とその環境下において、抗原との相互作用の結果、Induced-fitによる構造変化が誘起され、これが2回目以降の抗原暴露において、抗体の抗原認識を増強するのではないかという仮説を検証した。In vivoにおいても特異性を維持しながら、構造的な状況が変わることが示唆され、構造的免疫的記憶を実証した。