6OL7

Crystal structure of glVRC01 scFv in complex with anti-idiotype iv8 scFv

Summary for 6OL7

• Entry DOI: 10.2210/pdb6ol7/pdb
• Descriptor: iv8 Heavy Chain, glVRC01 Light Chain, glVRC01 Heavy Chain, ... (8 entities in total)
• Functional Keywords: glvrc01, iv8, anti-idiotype, scfv, antibody, hiv, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 16
• Total formula weight: 223425.73

Authors

Weidle, C.,Pancera, M. (deposition date: 2019-04-15, release date: 2019-07-24, Last modification date: 2023-10-11)

Primary citation

Dosenovic, P.,Pettersson, A.K.,Wall, A.,Thientosapol, E.S.,Feng, J.,Weidle, C.,Bhullar, K.,Kara, E.E.,Hartweger, H.,Pai, J.A.,Gray, M.D.,Parks, K.R.,Taylor, J.J.,Pancera, M.,Stamatatos, L.,Nussenzweig, M.C.,McGuire, A.T.
Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses.
J.Exp.Med., 216:2316-2330, 2019

PubMed Abstract: Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

PubMed: 31345931
DOI: 10.1084/jem.20190446

Experimental method

X-RAY DIFFRACTION (2.419 Å)