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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Avnir Y,Prachanronarong KL,Zhang Z,Hou S,Peterson EC,Sui J,Zayed H,Kurella VB,McGuire AT,Stamatatos L,Hilbert BJ,Bohn MF,Kowalik TF,Jensen JD,Finberg RW,Wang JP,Goodall M,Jefferis R,Zhu Q,Kurt Yilmaz N,Schiffer CAdoi
10.1016/j.celrep.2017.11.056subject
Has Abstractpub_date
2017-12-12 00:00:00pages
3243-3255issue
11issn
2211-1247pii
S2211-1247(17)31708-4journal_volume
21pub_type
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