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Title | Anti-idiotype isolation of a broad and potent influenza A virus-neutralizing human antibody. |
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Journal, issue, pages | Front Immunol, Vol. 15, Page 1399960, Year 2024 |
Publish date | May 30, 2024 |
Authors | Adam S Olia / Madhu Prabhakaran / Darcy R Harris / Crystal Sao-Fong Cheung / Rebecca A Gillespie / Jason Gorman / Abigayle Hoover / Nicholas C Morano / Amine Ourahmane / Abhinaya Srikanth / Shuishu Wang / Weiwei Wu / Tongqing Zhou / Sarah F Andrews / Masaru Kanekiyo / Lawrence Shapiro / Adrian B McDermott / Peter D Kwong / |
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 ...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. |
External links | Front Immunol / PubMed:38873606 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.78 - 3.95 Å |
Structure data | EMDB-43529, PDB-8vue: EMDB-43545, PDB-8vuz: PDB-8vvb: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN / influenza / hemagglutinin / antibody / ANTIVIRAL PROTEIN / anti-idiotype |