8VUE

L5A7 Fab bound to Indonesia2005 Hemagglutinin

Summary for 8VUE

• Entry DOI: 10.2210/pdb8vue/pdb
• EMDB information: 43529
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, L5A7 Fab Heavy Chain, ... (5 entities in total)
• Functional Keywords: influenza, hemagglutinin, antibody, viral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 312039.92

Authors

Olia, A.S.,Gorman, J.,Kwong, P.D. (deposition date: 2024-01-29, release date: 2024-05-22, Last modification date: 2025-05-21)

Primary citation

Olia, A.S.,Prabhakaran, M.,Harris, D.R.,Cheung, C.S.,Gillespie, R.A.,Gorman, J.,Hoover, A.,Morano, N.C.,Ourahmane, A.,Srikanth, A.,Wang, S.,Wu, W.,Zhou, T.,Andrews, S.F.,Kanekiyo, M.,Shapiro, L.,McDermott, A.B.,Kwong, P.D.
Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody.
Front Immunol, 15:1399960-1399960, 2024

PubMed Abstract: The VH6-1 class of antibodies includes some of the broadest and most potent antibodies that neutralize influenza A virus. Here, we elicit and isolate anti-idiotype antibodies against germline versions of VH6-1 antibodies, use these to sort human leukocytes, and isolate a new VH6-1-class member, antibody L5A7, which potently neutralized diverse group 1 and group 2 influenza A strains. While its heavy chain derived from the canonical IGHV6-1 heavy chain gene used by the class, L5A7 utilized a light chain gene, IGKV1-9, which had not been previously observed in other VH6-1-class antibodies. The cryo-EM structure of L5A7 in complex with Indonesia 2005 hemagglutinin revealed a nearly identical binding mode to other VH6-1-class members. The structure of L5A7 bound to the isolating anti-idiotype antibody, 28H6E11, revealed a shared surface for binding anti-idiotype and hemagglutinin that included two critical L5A7 regions: an FG motif in the third heavy chain-complementary determining region (CDR H3) and the CDR L1 loop. Surprisingly, the chemistries of L5A7 interactions with hemagglutinin and with anti-idiotype were substantially different. Overall, we demonstrate anti-idiotype-based isolation of a broad and potent influenza A virus-neutralizing antibody, revealing that anti-idiotypic selection of antibodies can involve features other than chemical mimicry of the target antigen.

PubMed: 38873606
DOI: 10.3389/fimmu.2024.1399960

Experimental method

ELECTRON MICROSCOPY (3.59 Å)