1. Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope
- Author
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Yuval Avnir, Kristina L. Prachanronarong, Zhen Zhang, Shurong Hou, Eric C. Peterson, Jianhua Sui, Hatem Zayed, Vinodh B. Kurella, Andrew T. McGuire, Leonidas Stamatatos, Brendan J. Hilbert, Markus-Frederik Bohn, Timothy F. Kowalik, Jeffrey D. Jensen, Robert W. Finberg, Jennifer P. Wang, Margaret Goodall, Roy Jefferis, Quan Zhu, Nese Kurt Yilmaz, Celia A. Schiffer, and Wayne A. Marasco
- Subjects
influenza ,anti-idiotypic antibody ,cross-reactive idiotype ,chronic lymphocytic leukemia ,VH germline genes ,IGHV polymorphism ,anti-influenza antibodies ,immunoglobulin germline genes ,crystal structure ,Biology (General) ,QH301-705.5 - Abstract
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.
- Published
- 2017
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