HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors.
HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors.
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HIV-1 VRC 01生殖系靶向免疫原选择不同的表位特异性B细胞受体。
DOI：
10.1016/j.immuni.2020.09.007
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发表时间：
2020-10-13
期刊：
影响因子：
32.4
通讯作者：
Stamatatos L
中科院分区：
文献类型：
--
作者：
Lin YR;Parks KR;Weidle C;Naidu AS;Khechaduri A;Riker AO;Takushi B;Chun JH;Borst AJ;Veesler D;Stuart A;Agrawal P;Gray M;Pancera M;Huang PS;Stamatatos L
激活HIV-1广泛中和抗体的前体B细胞受体需要专门设计的免疫原。在这里，我们比较了三种针对VRC 01类受体的生殖系靶向免疫原激活转基因小鼠中靶向B细胞的能力，所述转基因小鼠表达VRC 01抗体的生殖系VH但表达不同的小鼠轻链。在免疫后不同时间点分离免疫原特异性VRC 01样B细胞，对其VH/VL基因进行测序并表征相应的抗体。具有不同交叉反应性特性的VRC 01 B细胞亚群被每种免疫原激活，并且这些差异与生殖系靶向免疫原的不同生物物理和生物化学特征相关。我们的研究表明，设计有效的免疫原激活B细胞受体，导致保护性HIV-1抗体将需要更好地了解生物物理特性的表位及其周围的表面上的种系靶向免疫原影响其相互作用与可用的受体变体在体内。激活HIV-1广泛中和抗体的前体B细胞受体需要专门设计的免疫原。Lin，Parks等比较了三种针对VRC 01类受体的此类生殖系靶向免疫原，发现每种免疫原以不同的交叉反应性特性激活VRC 01 B细胞亚群，并且这些差异与生殖系靶向免疫原的不同生物物理和生物化学特征相关。
Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically-designed immunogens. Here, we compared the abilities of three such germline-targeting immunogens against the VRC01-class receptors to activate the targeted B cells in transgenic mice expressing the germline VH of the VRC01 antibody but diverse mouse light chains. Immunogen-specific VRC01-like B cells were isolated at different time points after immunization, their VH/VL genes were sequenced and the corresponding antibodies characterized. VRC01 B cell sub-populations with distinct cross-reactivity properties were activated by each immunogen, and these differences correlated with distinct biophysical and biochemical features of the germline-targeting immunogens. Our study indicates that the design of effective immunogens to activate B cell receptors leading to protective HIV-1 antibodies will require a better understanding of how the biophysical properties of the epitope and its surrounding surface on the germline-targeting immunogen influence its interaction with the available receptor variants in vivo. Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically-designed immunogens. Lin, Parks et al. compare three such germline-targeting immunogens against the VRC01-class receptors and find that each immunogen activates VRC01 B cell sub-populations with distinct cross-reactivity properties, and that these differences correlate with distinct biophysical and biochemical features of the germline-targeting immunogens.
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影响因子：
64.5
作者：
Briney, Bryan;Sok, Devin;Jardine, Joseph G.;Kulp, Daniel W.;Skog, Patrick;Menis, Sergey;Jacak, Ronald;Kalyuzhniy, Oleksandr;de Val, Natalia;Sesterhenn, Fabian;Le, Khoa M.;Ramos, Alejandra;Jones, Meaghan;Saye-Francisco, Karen L.;Blane, Tanya R.;Spencer, Skye;Georgeson, Erik;Hu, Xiaozhen;Ozorowski, Gabriel;Adachi, Yumiko;Kubitz, Michael;Sarkar, Anita;Wilson, Ian A.;Ward, Andrew B.;Nemazee, David;Burton, Dennis R.;Schief, William R.
通讯作者：
Schief, William R.
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
--
作者：
Giudicelli, Veronique;Brochet, Xavier;Lefranc, Marie-Paule
通讯作者：
Lefranc, Marie-Paule
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
64.5
作者：
Bonsignori M;Zhou T;Sheng Z;Chen L;Gao F;Joyce MG;Ozorowski G;Chuang GY;Schramm CA;Wiehe K;Alam SM;Bradley T;Gladden MA;Hwang KK;Iyengar S;Kumar A;Lu X;Luo K;Mangiapani MC;Parks RJ;Song H;Acharya P;Bailer RT;Cao A;Druz A;Georgiev IS;Kwon YD;Louder MK;Zhang B;Zheng A;Hill BJ;Kong R;Soto C;NISC Comparative Sequencing Program;Mullikin JC;Douek DC;Montefiori DC;Moody MA;Shaw GM;Hahn BH;Kelsoe G;Hraber PT;Korber BT;Boyd SD;Fire AZ;Kepler TB;Shapiro L;Ward AB;Mascola JR;Liao HX;Kwong PD;Haynes BF
通讯作者：
Haynes BF