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.
|Original language||English (US)|
|Journal||Journal of Experimental Medicine|
|State||Published - Dec 23 2020|
Bibliographical noteFunding 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).
© 2020 Lee et al.