October 23, 2019  |  

Structural determination of the broadly reactive anti-IGHV1-69 anti-idiotypic antibody G6 and its idiotope.

Authors: Avnir, Yuval and Prachanronarong, Kristina L and Zhang, Zhen and Hou, Shurong and Peterson, Eric C and Sui, Jianhua and Zayed, Hatem and Kurella, Vinodh B and McGuire, Andrew T and Stamatatos, Leonidas and Hilbert, Brendan J and Bohn, Markus-Frederik and Kowalik, Timothy F and Jensen, Jeffrey D and Finberg, Robert W and Wang, Jennifer P and Goodall, Margaret and Jefferis, Roy and Zhu, Quan and Kurt Yilmaz, Nese and Schiffer, Celia A and Marasco, Wayne A

The heavy chain IGHV1-69 germline gene exhibits a high level of polymorphism and shows biased use in protective antibody (Ab) responses to infections and vaccines. It is also highly expressed in several B cell malignancies and autoimmune diseases. G6 is an anti-idiotypic monoclonal Ab that selectively binds to IGHV1-69 heavy chain germline gene 51p1 alleles that have been implicated in these Ab responses and disease processes. Here, we determine the co-crystal structure of humanized G6 (hG6.3) in complex with anti-influenza hemagglutinin stem-directed broadly neutralizing Ab D80. The core of the hG6.3 idiotope is a continuous string of CDR-H2 residues starting with M53 and ending with N58. G6 binding studies demonstrate the remarkable breadth of binding to 51p1 IGHV1-69 Abs with diverse CDR-H3, light chain, and antigen binding specificities. These studies detail the broad expression of the G6 cross-reactive idiotype (CRI) that further define its potential role in precision medicine. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Journal: Cell reports
DOI: 10.1016/j.celrep.2017.11.056
Year: 2017

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