6ol7
From Proteopedia
Crystal structure of glVRC01 scFv in complex with anti-idiotype iv8 scFv
Structural highlights
Publication Abstract from PubMedHuman 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. Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses.,Dosenovic P, Pettersson AK, Wall A, Thientosapol ES, Feng J, Weidle C, Bhullar K, Kara EE, Hartweger H, Pai JA, Gray MD, Parks KR, Taylor JJ, Pancera M, Stamatatos L, Nussenzweig MC, McGuire AT J Exp Med. 2019 Jul 25. pii: jem.20190446. doi: 10.1084/jem.20190446. PMID:31345931[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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