UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Schiffer Lab; Department of Medicine; Department of Microbiology and Physiological Systems

Publication Date

2017-12-12

Document Type

Article

Disciplines

Biochemistry | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Structural Biology | Therapeutics

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

IGHV polymorphism, VH germline genes, anti-idiotypic antibody, anti-influenza antibodies, chronic lymphocytic leukemia, cross-reactive idiotype, crystal structure, immunoglobulin germline genes, influenza

Rights and Permissions

Copyright 2017 The Authors. Open Access funded by the US Department of Defense (DoD) or performed by an employee of DoD. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2017.11.056

Source

Cell Rep. 2017 Dec 12;21(11):3243-3255. doi: 10.1016/j.celrep.2017.11.056. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

29241550

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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