1. V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity
- Author
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Arshad Ismail, Barton F. Haynes, Tandile Hermanus, Molati Nonyane, Lynn Morris, M. Anthony Moody, Heini W. Dirr, Valerie Bekker, Constantinos Kurt Wibmer, Salim S. Abdool Karim, Yasien Sayed, Balakrishnan Vijayakumar, Sherry Stanfield-Oakley, Nonhlanhla N. Mkhize, Lawrence Shapiro, Jinal N. Bhiman, Nigel Garrett, Batsirai Mabvakure, Zizhang Sheng, Penny L. Moore, Bronwen E. Lambson, Simone I. Richardson, Manuel A. Fernandes, Kevin Wiehe, Guido Ferrari, Charmaine. van Eeden, and Cathrine Scheepers
- Subjects
0301 basic medicine ,Models, Molecular ,HIV Infections ,Biology ,HIV Antibodies ,HIV Envelope Protein gp120 ,Immunoglobulin light chain ,General Biochemistry, Genetics and Molecular Biology ,Germline ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Humans ,030212 general & internal medicine ,Amino Acid Sequence ,Cytotoxicity ,Gene ,lcsh:QH301-705.5 ,Alleles ,Antibody-dependent cell-mediated cytotoxicity ,AIDS Vaccines ,Lysine ,Vaccine trial ,Antibody-Dependent Cell Cytotoxicity ,Virology ,Tissue Donors ,3. Good health ,030104 developmental biology ,lcsh:Biology (General) ,biology.protein ,Immunoglobulin Light Chains ,Antibody ,Peptides ,Protein Binding - Abstract
SUMMARY 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., In Brief V2-directed antibodies from the RV144 vaccine trial correlated with reduced HIV-1 infection risk but exhibited restricted light chain gene usage. Here, van Eeden et al. isolate similar antibodies from an HIV-1-infected individual and identify a third V2-reactive light chain gene, increasing the antibody repertoire potentially elicited by vaccination., Graphical Abstract
- Published
- 2018