6fy0

Publication Abstract from PubMed

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.

V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.,van Eeden C, Wibmer CK, Scheepers C, Richardson SI, Nonyane M, Lambson B, Mkhize NN, Vijayakumar B, Sheng Z, Stanfield-Oakley S, Bhiman JN, Bekker V, Hermanus T, Mabvakure B, Ismail A, Moody MA, Wiehe K, Garrett N, Karim SA, Dirr H, Fernandes MA, Sayed Y, Shapiro L, Ferrari G, Haynes BF, Moore PL, Morris L Cell Rep. 2018 Dec 11;25(11):3123-3135.e6. doi: 10.1016/j.celrep.2018.11.058. PMID:30540944^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.