Preferential use of the VH5-51 gene segment by the human immune response to code for antibodies against the V3 domain of HIV-1

被引:82
|
作者
Gorny, Miroslaw K. [1 ]
Wang, Xiao-Hong [3 ]
Williams, Constance [1 ]
Volsky, Barbara [1 ]
Revesz, Kathy [3 ]
Witover, Bradley [1 ]
Burda, Sherri [1 ]
Urbanski, Mateusz [1 ]
Nyambi, Phillipe [1 ,3 ]
Krachmarov, Chavdar [4 ]
Pinter, Abraham [4 ]
Zolla-Pazner, Susan [1 ,3 ]
Nadas, Arthur [2 ]
机构
[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA
[2] NYU, Sch Med, Inst Environm Med, New York, NY 10016 USA
[3] Vet Affairs New York Harbor Healthcare Syst, New York, NY 10010 USA
[4] Publ Hlth Res Inst, Newark, NJ 07103 USA
关键词
Immunoglobulin gene usage; Human monoclonal antibodies; Anti-HIV-1; antibodies; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; EXTENSIVE SOMATIC MUTATION; POLYMERASE-CHAIN-REACTION; EQUATORIAL RAIN-FORESTS; MEMORY B-CELLS; MOLECULAR CHARACTERIZATION; TYPE-1; GP120; CORECEPTOR SELECTIVITY; ENVELOPE GLYCOPROTEIN;
D O I
10.1016/j.molimm.2008.09.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human anti-V3 monoclonal antibodies (mAbs) generated from HIV-1 infected individuals display diversity in the range of their cross-neutralization that may be related to their immunogenetic background. The study of the immunoglobulin (Ig) variable region gene usage of heavy chains have shown a preferential usage of the VH5-51 gene segment which was detected in 35% of 51 human anti-V3 mAbs. In contrast, human mAbs against other envelope regions of HIV-1 (anti-Env), including the CD4-binding domain, the CD4-induced epitope, and gp41 preferentially used the VH1-69 gene segment, and none of them used the VH5-51 gene, Furthermore, the usage of the VH4 family by anti-V3 mAbs was restricted to only one gene segment, VH4-59, while the VH3 gene family was used at a significantly lower frequency by all of the analyzed anti-HIV-1 mAbs. Multivariate analysis showed that usage of VH gene segments was significantly different between anti-V3 and anti-Env mAbs, and compared to antibodies from healthy subjects. In addition, the anti-V3 mAbs preferentially used the JH3 and D2-15 gene segments. The preferential usage of selected Ig gene segments and the characteristic pattern of Ig gene usage by anti-V3 mAbs can be related to the conserved structure of the V3 region. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:917 / 926
页数:10
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