Broder C C, Earl P L, Long D, Abedon S T, Moss B, Doms R W
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11699-703. doi: 10.1073/pnas.91.24.11699.
A majority of monoclonal antibodies (mAbs) raised against soluble oligomeric human immunodeficiency virus type 1 isolate IIIB (HIV-1IIIB) envelope (env) glycoprotein reacted with conformational epitopes within the gp120 or gp41 subunits. Of 35 mAbs directed against gp41, 21 preferentially reacted with oligomeric env. A subset of these mAbs reacted only with env oligomers (oligomer-specific mAbs). In contrast, only 1 of 27 mAbs directed against the gp120 subunit reacted more strongly with env oligomers than with monomers, and none were oligomer-specific. However, 50% of anti-gp120 mAbs preferentially recognized monomeric env, suggesting that some epitopes in gp120 are partially masked or altered by intersubunit contacts in the native env oligomer. Two mAbs to oligomer-dependent epitopes in gp41 neutralized HIV-1IIIB and HIV-1SF2, and binding of these mAbs to env was blocked by preincubation with HIV-1-positive human serum. Thus, immunization with soluble, oligomeric env elicits antibodies to conserved, conformational epitopes including a newly defined class of neutralizing antibodies that bind to oligomer-specific epitopes in gp41, and may also minimize the production of antibodies that preferentially react with monomeric env protein.
大多数针对可溶性寡聚体1型人类免疫缺陷病毒IIIB株（HIV-1IIIB）包膜（env）糖蛋白产生的单克隆抗体（mAb）与gp120或gp41亚基内的构象表位发生反应。在35种针对gp41的单克隆抗体中，有21种优先与寡聚体env发生反应。这些单克隆抗体的一个亚组仅与env寡聚体发生反应（寡聚体特异性单克隆抗体）。相比之下，在27种针对gp120亚基的单克隆抗体中，只有1种与env寡聚体的反应比与单体的反应更强，且没有一种是寡聚体特异性的。然而，50%的抗gp120单克隆抗体优先识别单体env，这表明gp120中的一些表位在天然env寡聚体中被亚基间接触部分掩盖或改变。两种针对gp41中寡聚体依赖性表位的单克隆抗体可中和HIV-1IIIB和HIV-1SF2，并且这些单克隆抗体与env的结合可通过与HIV-1阳性人血清预孵育来阻断。因此，用可溶性寡聚体env进行免疫可引发针对保守构象表位的抗体，包括一类新定义的中和抗体，它们可结合gp41中的寡聚体特异性表位，并且还可能减少优先与单体env蛋白发生反应的抗体的产生。
