Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope

被引：17

作者：

Avnir, Yuval ^{[1
,2
]}

Prachanronarong, Kristina L. ^{[3
]}

Zhang, Zhen ^{[1
,2
]}

Hou, Shurong ^{[3
]}

Peterson, Eric C. ^{[1
,2
]}

Sui, Jianhua ^{[1
,2
]}

Zayed, Hatem ^{[1
,2
]}

Kurella, Vinodh B. ^{[1
,2
]}

McGuire, Andrew T. ^{[4
]}

Stamatatos, Leonidas ^{[4
]}

Hilbert, Brendan J. ^{[3
]}

Bohn, Markus-Frederik ^{[3
]}

Kowalik, Timothy F. ^{[6
]}

Jensen, Jeffrey D. ^{[7
]}

Finberg, Robert W. ^{[5
]}

Wang, Jennifer P. ^{[5
]}

Goodall, Margaret ^{[8
]}

Jefferis, Roy ^{[8
]}

Zhu, Quan ^{[1
,2
]}

Yilmaz, Nese Kurt ^{[3
]}

Schiffer, Celia A. ^{[3
]}

Marasco, Wayne A. ^{[1
,2
]}

机构：

[1] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[3] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01655 USA

[4] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

[5] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA

[6] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA USA

[7] Arizona State Univ, Sch Life Sci, Ctr Evolut & Med, Tempe, AZ USA

[8] Univ Birmingham, Coll Med & Dent Sci, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England

来源：

CELL REPORTS | 2017年 / 21卷 / 11期

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; INDIVIDUAL ANTIGENIC SPECIFICITY; V-H GENES; IMMUNOGLOBULIN HEAVY; B-CELLS; NEUTRALIZING ANTIBODIES; RABBIT ANTIBODIES; MERS-COV; CHAIN; INFLUENZA;

D O I：

10.1016/j.celrep.2017.11.056

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：3243 / 3255

页数：13

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