Cell Reports (Dec 2017)
Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope
- 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
Affiliations
- Yuval Avnir
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Kristina L. Prachanronarong
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Zhen Zhang
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Shurong Hou
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Eric C. Peterson
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Jianhua Sui
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Hatem Zayed
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Vinodh B. Kurella
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Andrew T. McGuire
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Leonidas Stamatatos
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Brendan J. Hilbert
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Markus-Frederik Bohn
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Timothy F. Kowalik
- Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA
- Jeffrey D. Jensen
- School of Life Sciences, Center for Evolution and Medicine, Arizona State University, Tempe, AZ, USA
- Robert W. Finberg
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
- Jennifer P. Wang
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
- Margaret Goodall
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Roy Jefferis
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Quan Zhu
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- Nese Kurt Yilmaz
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Celia A. Schiffer
- Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA
- Wayne A. Marasco
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA
- DOI
- https://doi.org/10.1016/j.celrep.2017.11.056
- Journal volume & issue
-
Vol. 21,
no. 11
pp. 3243 – 3255
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.
Keywords
- influenza
- anti-idiotypic antibody
- cross-reactive idiotype
- chronic lymphocytic leukemia
- VH germline genes
- IGHV polymorphism
- anti-influenza antibodies
- immunoglobulin germline genes
- crystal structure
