Sok Devin, Pauthner Matthias, Briney Bryan, Lee Jeong Hyun, Saye-Francisco Karen L, Hsueh Jessica, Ramos Alejandra, Le Khoa M, Jones Meaghan, Jardine Joseph G, Bastidas Raiza, Sarkar Anita, Liang Chi-Hui, Shivatare Sachin S, Wu Chung-Yi, Schief William R, Wong Chi-Huey, Wilson Ian A, Ward Andrew B, Zhu Jiang, Poignard Pascal, Burton Dennis R
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, New York, NY 10004, USA.
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA.
Immunity. 2016 Jul 19;45(1):31-45. doi: 10.1016/j.immuni.2016.06.026.
The dense patch of high-mannose-type glycans surrounding the N332 glycan on the HIV envelope glycoprotein (Env) is targeted by multiple broadly neutralizing antibodies (bnAbs). This region is relatively conserved, implying functional importance, the origins of which are not well understood. Here we describe the isolation of new bnAbs targeting this region. Examination of these and previously described antibodies to Env revealed that four different bnAb families targeted the (324)GDIR(327) peptide stretch at the base of the gp120 V3 loop and its nearby glycans. We found that this peptide stretch constitutes part of the CCR5 co-receptor binding site, with the high-mannose patch glycans serving to camouflage it from most antibodies. GDIR-glycan bnAbs, in contrast, bound both (324)GDIR(327) peptide residues and high-mannose patch glycans, which enabled broad reactivity against diverse HIV isolates. Thus, as for the CD4 binding site, bnAb effectiveness relies on circumventing the defenses of a critical functional region on Env.
HIV包膜糖蛋白（Env）上围绕N332聚糖的高甘露糖型聚糖密集区域是多种广谱中和抗体（bnAbs）的作用靶点。该区域相对保守，暗示其具有功能重要性，但其起源尚不清楚。在此，我们描述了针对该区域的新型bnAbs的分离。对这些以及先前描述的Env抗体的研究表明，四个不同的bnAb家族靶向gp120 V3环底部的（324）GDIR（327）肽段及其附近的聚糖。我们发现，该肽段构成CCR5共受体结合位点的一部分，高甘露糖补丁聚糖可将其大部分抗体掩盖。相比之下，GDIR-聚糖bnAbs既能结合（324）GDIR（327）肽段残基，也能结合高甘露糖补丁聚糖，从而对多种HIV分离株具有广泛的反应性。因此，就像CD4结合位点一样，bnAb的有效性依赖于规避Env上关键功能区域的防御机制。
