Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers
Open Access
- 23 December 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 218 (2)
- https://doi.org/10.1084/jem.20201254
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.Funding Information
- National Institutes of Health (AI100663, AI144462, R01 AI143826)
- Collaboration for AIDS Vaccine Discovery
- National Institutes of Health (S10 RR027366)
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