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

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

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

机译：调节HIV ENV特异性CD4 T细胞的量，促进生发中心的稀有B细胞应答

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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.

机译：非中和表位的免疫优势是设计针对几种高度关注的疾病的疫苗的障碍。一种假设的可能性是，在正常的生发中心（GC）反应中，有限的CD4 T细胞有助于B细胞，导致大量免疫优势B细胞的选择性招募。这是HIV包膜糖蛋白（Env）疫苗设计中的一个核心问题，因为广泛中和表位的前体很少见。在这里，我们试图阐明调节T细胞帮助的数量是否会影响广泛中和抗体前体B细胞的招募和竞争，以生理前体频率响应Env三聚体免疫。为了做到这一点，两个新的环境特异性CD4转基因（Tg）T细胞受体（TCR）小鼠系被产生，携带来自环境蛋白免疫的TCR对。我们的结果表明，CD4 T细胞有助于定量调节罕见B细胞向GCs的早期募集。

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《The British journal of psychiatry :》 |2021年第2期|共20页
作者
Lee Jeong Hyun; Hu Joyce K.; Georgeson Erik; Nakao Catherine; Groschel Bettina; Dileepan Thamotharampillai; Jenkins Marc K.; Seumois Gregory; Vijayanand Pandurangan; Schief William R.; Crotty Shane;
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作者单位

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

Scripps Res Inst Consortium HIV AIDS Vaccine Dev La Jolla CA 92037 USA;

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

Scripps Res Inst Consortium HIV AIDS Vaccine Dev La Jolla CA 92037 USA;

Univ Minnesota Ctr Immunol Dept Microbiol &

Immunol Med Sch Minneapolis MN USA;

Univ Minnesota Ctr Immunol Dept Microbiol &

Immunol Med Sch Minneapolis MN USA;

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

Scripps Res Inst Consortium HIV AIDS Vaccine Dev La Jolla CA 92037 USA;

La Jolla Inst Immunol Ctr Infect Dis &

Vaccine Res La Jolla CA 92037 USA;

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正文语种 eng
中图分类精神病学;
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机译：调节HIV Env特异性CD4 T细胞的量帮助促进生发中心的稀有B细胞应答
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机译：先天性和适应性免疫应答均有助于HIV-1感染乌干达人的病理性CD4 T细胞活化

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

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