Modulating the quantity of HIV Env-specific CD4 T cell help promotes rare B cell responses in germinal centers
Jeong Hyun Lee, Joyce Hu, Erik Georgeson, Catherine Nakao, Bettina Gröschel, Thamotharampillai Dileepan, Marc K. Jenkins, Grégory Seumois, Pandurangan Vijayanand, William R. Schief, Shane Crotty
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.