Download MendeleyV2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.
van Eeden, C., Wibmer, C.K., Scheepers, C., Richardson, S.I., Nonyane, M., Lambson, B., Mkhize, N.N., Vijayakumar, B., Sheng, Z., Stanfield-Oakley, S., Bhiman, J.N., Bekker, V., Hermanus, T., Mabvakure, B., Ismail, A., Moody, M.A., Wiehe, K., Garrett, N., Karim, S.A., Dirr, H., Fernandes, M.A., Sayed, Y., Shapiro, L., Ferrari, G., Haynes, B.F., Moore, P.L., Morris, L.(2018) Cell Rep 25: 3123-3135.e6
- PubMed: 30540944
- DOI: https://doi.org/10.1016/j.celrep.2018.11.058
- Primary Citation of Related Structures:
6FY0 - PubMed 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.
Organizational Affiliation:
National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.
