Elucidation of the molecular recognition of stereotype rheumatoid factor.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06514
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Shiroishi Mitsunori 東京理科大学, 先進工学部生命システム工学科, 准教授 (00380527)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: リウマトイド因子 / 自己抗体 / 分子認識 / 構造解析

Outline of Final Research Achievements

We have established a large-scale preparation system for YES8c, which is a rheumatoid factor (RF) derived from IGHV1-69, and RF-SJ1, which is an RF derived from TS1 and IGHV3-30, in the Fv-clasp format. YES8c Fv-clasp showed the same binding property as its Fab. On the other hand, Fv-clasp of RF-TS1 showed different binding in ELISA and SPR analysis. It is suggested that this may be due to the antigen recognition mechanism due to the weak affinity between the H chain and the L chain. For YES8c, it was suggested that the N-terminal of the L chain is involved in antigen recognition.

Free Research Field

タンパク質科学，構造生物学，生物物理学

Academic Significance and Societal Importance of the Research Achievements

ステレオタイプリウマトイド因子（RF）の元になる抗体の生殖系列遺伝子は、ウィルスや細菌毒素の中和抗体として頻繁に使われることが分かっており、慢性炎症と密接に関係していると言われている。ステレオタイプRFの普遍的な分子認識メカニズムを構造学的に明らかにすることで、慢性炎症から発展する種々の血液疾患に適した治療法の開発などに有益な情報をもたらすことが期待できる。