Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope
oleh: 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, Wayne A. Marasco
| Format: | Article |
|---|---|
| Diterbitkan: | Elsevier 2017-12-01 |
Deskripsi
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.