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Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers

Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers
Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers

Immunodominance to nonneutralizing epitopes is a roadblock in designing vaccines against several diseases of high interest. One hypothetical possibility is that limited CD4 T cell help to B cells in a normal germinal center (GC) response results in selective recruitment of abundant, immunodominant B cells. This is a central issue in HIV envelope glycoprotein (Env) vaccine designs, because precursors to broadly neutralizing epitopes are rare. Here, we sought to elucidate whether modulating the quantity of T cell help can influence recruitment and competition of broadly neutralizing antibody precursor B cells at a physiological precursor frequency in response to Env trimer immunization. To do so, two new Env-specific CD4 transgenic (Tg) T cell receptor (TCR) mouse lines were generated, carrying TCR pairs derived from Env-protein immunization. Our results suggest that CD4 T cell help quantitatively regulates early recruitment of rare B cells to GCs.

0022-1007
Lee, Jeong Hyun
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Hu, Joyce K.
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Georgeson, Erik
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Nakao, Catherine
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Groschel, Bettina
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Dileepan, Thamotharampillai
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Jenkins, Marc K.
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Seumois, Gregory
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Vijayanand, Pandurangan
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Schief, William R.
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Crotty, Shane
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Lee, Jeong Hyun
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Hu, Joyce K.
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Georgeson, Erik
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Nakao, Catherine
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Groschel, Bettina
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Dileepan, Thamotharampillai
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Jenkins, Marc K.
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Seumois, Gregory
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Vijayanand, Pandurangan
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Schief, William R.
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Crotty, Shane
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Lee, Jeong Hyun, Hu, Joyce K., Georgeson, Erik, Nakao, Catherine, Groschel, Bettina, Dileepan, Thamotharampillai, Jenkins, Marc K., Seumois, Gregory, Vijayanand, Pandurangan, Schief, William R. and Crotty, Shane (2020) Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers. Journal of Experimental Medicine, 218 (2), [e20201254]. (doi:10.1084/JEM.20201254).

Record type: Article

Abstract

Immunodominance to nonneutralizing epitopes is a roadblock in designing vaccines against several diseases of high interest. One hypothetical possibility is that limited CD4 T cell help to B cells in a normal germinal center (GC) response results in selective recruitment of abundant, immunodominant B cells. This is a central issue in HIV envelope glycoprotein (Env) vaccine designs, because precursors to broadly neutralizing epitopes are rare. Here, we sought to elucidate whether modulating the quantity of T cell help can influence recruitment and competition of broadly neutralizing antibody precursor B cells at a physiological precursor frequency in response to Env trimer immunization. To do so, two new Env-specific CD4 transgenic (Tg) T cell receptor (TCR) mouse lines were generated, carrying TCR pairs derived from Env-protein immunization. Our results suggest that CD4 T cell help quantitatively regulates early recruitment of rare B cells to GCs.

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jem_20201254 - Version of Record
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Accepted/In Press date: 13 November 2020
Published date: 23 December 2020
Additional Information: Funding Information: This work was funded in part by the National Institutes of Health (AI100663, Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and AI144462, Scripps Consortium for HIV/AIDS Vaccine Development, to S. Crotty and W.R. Schief; R01 AI143826 to M.K. Jenkins) and the Collaboration for AIDS Vaccine Discovery (funding from the International AIDS Vaccine Initiative Neutralizing Antibody Center toW.R. Schief). The FACSAria II Cell Sorter was acquired through the National Institutes of Health Shared Instrumentation Grant Program (S10 RR027366). Publisher Copyright: © 2020 Lee et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 453733
URI: http://eprints.soton.ac.uk/id/eprint/453733
ISSN: 0022-1007
PURE UUID: f7674f4f-630f-41f8-a057-2de0cce257d6
ORCID for Pandurangan Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

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Date deposited: 21 Jan 2022 17:42
Last modified: 17 Mar 2024 12:54

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Contributors

Author: Jeong Hyun Lee
Author: Joyce K. Hu
Author: Erik Georgeson
Author: Catherine Nakao
Author: Bettina Groschel
Author: Thamotharampillai Dileepan
Author: Marc K. Jenkins
Author: Gregory Seumois
Author: Pandurangan Vijayanand ORCID iD
Author: William R. Schief
Author: Shane Crotty

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