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. G6 is an exceptional anti-idiotypic antibody that binds to antibodies encoded by the immunoglobulin heavy chain germline gene IGHV1-69. Yuval et al. describe how G6 binds to its cross-reactive idiotope by a set of binding assays and by solving the structure of humanized-G6 complexed with an IGHV1-69-anti-influenza Ab.
Original language | English (US) |
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Pages (from-to) | 3243-3255 |
Number of pages | 13 |
Journal | Cell Reports |
Volume | 21 |
Issue number | 11 |
DOIs | |
State | Published - Dec 12 2017 |
Keywords
- IGHV polymorphism
- VH germline genes
- anti-idiotypic antibody
- anti-influenza antibodies
- chronic lymphocytic leukemia
- cross-reactive idiotype
- crystal structure
- immunoglobulin germline genes
- influenza
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)