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第3日　5月13日（水）　15:50～16:10　B会場（1202）

3B-O14-1550（2P-45）　　PDF

水素/重水素交換質量分析によるIgG1とFcγRIIIaの相互作用解析

(¹阪大院工・ ²名市大院薬・ ³ExCELLS・ ⁴産総研創薬基盤・ ⁵徳大院社会産業理工・ ⁶サーモフィッシャー・ ⁷名大院理)
^o山口祐希¹・ 與語理那^2,3・ 渡辺大輝³・ 矢木宏和²・ 佐藤匡史²・ 中西真人⁴・ 鬼塚正義⁵・ 大政健史¹・ 若泉なつみ¹・ 嶋田麻里¹・ 丸野孝浩¹・ 鳥巣哲生¹・ 渡邊史生⁶・ 肥後大輔⁶・ 内橋貴之^3,7・ 谷中冴子^2,3・ 加藤晃一^2,3・ 内山進^1,3

Interaction of immunoglobulin G1 (IgG1) and FcγRIIIa expressed on the natural killer cells promotes antibody-dependent cellular cytotoxicity (ADCC). In previous studies, the structure of the IgG Fc fragments and FcγRIII complex has been reported, however, the complex structure of IgG full-body and FcγRIII remains elusive. Here, we performed hydrogen/deuterium exchange mass spectrometry (HDX-MS) to identify the interaction sites between IgG1 full-body and FcγRIIIa. HDX-MS monitors chronological HDX rates of amide hydrogens by MS-based peptide mapping which is used for measuring the mass shift caused by HDX. HDX of the interacting regions in complex state were slower than free state. Comparison of HDX in IgG1 with that in IgG1-FcγRIIIa complex showed that HDX rates of some segments in the Fab region decreased upon the binding to FcγRIIIa as well as the previously reported binding site in the Fc region. For FcγRIIIa, changes in HDX rate were observed in some regions in domain 1 by the binding to IgG1. These results indicate that not only the Fc region of IgG1 but also the Fab region are responsible for the binding of IgG1 to FcγR. Our findings will offer the new target for the developments of ADCC-enhanced therapeutic antibodies