Dataset Information

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

ABSTRACT: Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. A cocrystal structure of CAP228-16H bound to a V2 peptide identified a IGLV3-21 gene-encoded DDxD motif that is used to bind K169, with a mechanism that allows CAP228-16H to recognize more globally relevant V2 immunotypes. Overall, these data further our understanding of the development of cross-reactive, V2-binding, antiviral antibodies and effectively expand the human light chain repertoire able to respond to RV144-like immunogens.

SUBMITTER: van Eeden C

PROVIDER: S-EPMC6342559 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

van Eeden Charmaine C Wibmer Constantinos Kurt CK Scheepers Cathrine C Richardson Simone I SI Nonyane Molati M Lambson Bronwen B Mkhize Nonhlanhla N NN Vijayakumar Balakrishnan B Sheng Zizhang Z Stanfield-Oakley Sherry S Bhiman Jinal N JN Bekker Valerie V Hermanus Tandile T Mabvakure Batsirai B Ismail Arshad A Moody M Anthony MA Wiehe Kevin K Garrett Nigel N Karim Salim Abdool SA Dirr Heini H Fernandes Manuel A MA Sayed Yasien Y Shapiro Lawrence L Ferrari Guido G Haynes Barton F BF Moore Penny L PL Morris Lynn L

Cell reports 20181201 11

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to ...[more]

PMID: 30540944

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Dataset Information

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Publications

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Similar Datasets

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