Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses
The V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is one of the conserved immunogenic regions targeted by neutralizing antibodies (nAb). Two different binding modes of anti-V3 abs have been reported in studies using two V3 mimotopes: the ladle-type and cradle-type...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Virology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fviro.2022.932187/full |
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| author | Yu Kaku Kaho Matsumoto Takeo Kuwata Hasan Md Zahid Shashwata Biswas Miroslaw K. Gorny Shuzo Matsushita |
| author_facet | Yu Kaku Kaho Matsumoto Takeo Kuwata Hasan Md Zahid Shashwata Biswas Miroslaw K. Gorny Shuzo Matsushita |
| author_sort | Yu Kaku |
| collection | DOAJ |
| description | The V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is one of the conserved immunogenic regions targeted by neutralizing antibodies (nAb). Two different binding modes of anti-V3 abs have been reported in studies using two V3 mimotopes: the ladle-type and cradle-type. We previously isolated a ladle-type nAb, 1C10, that potently and broadly neutralized clade B viruses. Despite its potent neutralization activity, 1C10 possesses no unique features in its amino acid sequence. We hypothesized that the neutralization potency of 1C10 is derived from its antigen-binding characteristics, which are not a consequence of the two previously reported binding modes of anti-V3 nAbs. To analyze epitope-paratope interactions between 1C10 and the V3 loop, we produced five anti-idiotypic antibodies (anti-Id abs) from mice immunized with 1C10 nAb. The idiotopes of the anti-Id Abs on the 1C10 heavy chain were estimated by alanine scanning, germline reversion mutagenesis, and a 1C10 sibling clone. Next-generation sequencing combined with homology modeling revealed contact between R315 at the tip of the V3 loop and 1C10 by D53 of CDRH2 and Phe/Asp of CDRH3. These amino acids were enriched in the anti-Id-ab-reactive B cell receptors encoded by the IGHV3-30 gene. We also found that 20% of HIV-infected individuals had abs specific to the anti-Id abs, as well as both of the V3 mimotopes, that did not respond to the linear V3 peptide. Our findings showed that the anti-Id abs induced by 1C10 recognized a key amino acid formation essential for steric interactions between the ladle-type nAb and the V3 loop. We also revealed the coexistence of anti-V3 ab reactivity to V3 loop mimotopes and to the anti-Id abs in HIV-positive individuals. |
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| language | English |
| last_indexed | 2024-04-12T18:33:31Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-f6e462b2b5cf4ef491c08cf908dfbdc82022-12-22T03:21:01ZengFrontiers Media S.A.Frontiers in Virology2673-818X2022-08-01210.3389/fviro.2022.932187932187Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B virusesYu Kaku0Kaho Matsumoto1Takeo Kuwata2Hasan Md Zahid3Shashwata Biswas4Miroslaw K. Gorny5Shuzo Matsushita6Clinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanClinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanClinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanClinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanClinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanDepartment of Pathology, New York University (NYU) School of Medicine, New York, NY, United StatesClinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, JapanThe V3 loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) is one of the conserved immunogenic regions targeted by neutralizing antibodies (nAb). Two different binding modes of anti-V3 abs have been reported in studies using two V3 mimotopes: the ladle-type and cradle-type. We previously isolated a ladle-type nAb, 1C10, that potently and broadly neutralized clade B viruses. Despite its potent neutralization activity, 1C10 possesses no unique features in its amino acid sequence. We hypothesized that the neutralization potency of 1C10 is derived from its antigen-binding characteristics, which are not a consequence of the two previously reported binding modes of anti-V3 nAbs. To analyze epitope-paratope interactions between 1C10 and the V3 loop, we produced five anti-idiotypic antibodies (anti-Id abs) from mice immunized with 1C10 nAb. The idiotopes of the anti-Id Abs on the 1C10 heavy chain were estimated by alanine scanning, germline reversion mutagenesis, and a 1C10 sibling clone. Next-generation sequencing combined with homology modeling revealed contact between R315 at the tip of the V3 loop and 1C10 by D53 of CDRH2 and Phe/Asp of CDRH3. These amino acids were enriched in the anti-Id-ab-reactive B cell receptors encoded by the IGHV3-30 gene. We also found that 20% of HIV-infected individuals had abs specific to the anti-Id abs, as well as both of the V3 mimotopes, that did not respond to the linear V3 peptide. Our findings showed that the anti-Id abs induced by 1C10 recognized a key amino acid formation essential for steric interactions between the ladle-type nAb and the V3 loop. We also revealed the coexistence of anti-V3 ab reactivity to V3 loop mimotopes and to the anti-Id abs in HIV-positive individuals.https://www.frontiersin.org/articles/10.3389/fviro.2022.932187/fullHIV-1neutralizing antibodyvaccineanti-idiotypic antibodyanti-V3 antibody |
| spellingShingle | Yu Kaku Kaho Matsumoto Takeo Kuwata Hasan Md Zahid Shashwata Biswas Miroslaw K. Gorny Shuzo Matsushita Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses Frontiers in Virology HIV-1 neutralizing antibody vaccine anti-idiotypic antibody anti-V3 antibody |
| title | Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses |
| title_full | Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses |
| title_fullStr | Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses |
| title_full_unstemmed | Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses |
| title_short | Development and characterization of a panel of anti-idiotype antibodies to 1C10 that cross-neutralize HIV-1 subtype B viruses |
| title_sort | development and characterization of a panel of anti idiotype antibodies to 1c10 that cross neutralize hiv 1 subtype b viruses |
| topic | HIV-1 neutralizing antibody vaccine anti-idiotypic antibody anti-V3 antibody |
| url | https://www.frontiersin.org/articles/10.3389/fviro.2022.932187/full |
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