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.
Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers
Disclosures: M.K. Jenkins reported a patent to US2019/044605 issued. W.R. Schief reported grants from Compuvax, Inc outside the submitted work; in addition, W.R. Schief had a patent to BG505 GT3.1 pending and a patent to BG505 MD39 pending. No other disclosures were reported.
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Jeong Hyun Lee, Joyce K. Hu, Erik Georgeson, Catherine Nakao, Bettina Groschel, Thamotharampillai Dileepan, Marc K. Jenkins, Gregory Seumois, Pandurangan Vijayanand, William R. Schief, Shane Crotty; Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers. J Exp Med 1 February 2021; 218 (2): e20201254. doi: https://doi.org/10.1084/jem.20201254
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