Ghetie V, Slaughter C, Wheeler H T, Uhr J W, Vitetta E S
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048.
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5690-3. doi: 10.1073/pnas.88.13.5690.
Sera from human immunodeficiency virus-positive (HIV+; Walter Reed stage 6) individuals inhibit the interaction between recombinant human CD4 and recombinant gp120 from HIV (rCD4 and rgp120, respectively), thereby interfering with the ability of soluble rCD4 to block infection with HIV or rCD4-toxin conjugates to kill HIV-infected cells. In this report we demonstrate that the inhibitory activity of such sera is caused primarily by anti-gp120 antibodies that do not recognize the CD4 interaction site on gp120. To circumvent the problem of inhibition, we have generated a construct containing a peptide of CD4 (residues 41-84) conjugated to ovalbumin (three to five peptides per molecule). This multivalent conjugate binds to rgp120 and binding is not inhibited by antibodies in HIV+ sera.
来自人类免疫缺陷病毒阳性(HIV+;沃尔特·里德6期)个体的血清会抑制重组人CD4与HIV重组gp120(分别为rCD4和rgp120)之间的相互作用,从而干扰可溶性rCD4阻断HIV感染的能力或rCD4-毒素偶联物杀死HIV感染细胞的能力。在本报告中,我们证明此类血清的抑制活性主要由不识别gp120上CD4相互作用位点的抗gp120抗体引起。为了规避抑制问题,我们构建了一种包含与卵清蛋白偶联的CD4肽(第41-84位氨基酸残基)的构建体(每个分子含三到五个肽)。这种多价偶联物可与rgp120结合,且HIV+血清中的抗体不会抑制其结合。