Trujillo J R, Rogers R A, Brain J D
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Virology. 1998 Jun 20;246(1):53-62. doi: 10.1006/viro.1998.9185.
Proliferation of HIV-1 in the infected host is characterized by a progressive loss of CD4+ T lymphocytes and consequent dysregulation of the immune system. Both direct and indirect mechanisms have been proposed. We show here that proteins with molecular weights 35, 48, and 110 kDa on stimulated primary human T cells are recognized by neutralizing antibodies against the V3 loop of HIV-1 gp120. Recognition is specific since it can be blocked by a recombinant HIV-1 gp120. Furthermore, these V3 monoclonal antibodies, as well as sera from AIDS patients that recognized these V3-like proteins, induced killing of HIV-1-infected as well as uninfected T cells. This killing was also inhibited by HIV-1 gp120 V3 peptides. These results indicate that the V3 loop shares epitopes with proteins on stimulated T cells. This may be an additional autoimmune mechanism contributing to CD4+ T cell disappearance in AIDS. V3 antibodies have been proposed as potential prophylactic agents. However, if such vaccines were based on certain epitopes, they might induce cross-reacting immune responses with cellular proteins. Vaccine candidates should be evaluated for such potential effects.
HIV-1在受感染宿主中的增殖表现为CD4+ T淋巴细胞逐渐减少以及随之而来的免疫系统失调。已经提出了直接和间接机制。我们在此表明，刺激的原代人T细胞上分子量为35、48和110 kDa的蛋白质可被针对HIV-1 gp120 V3环的中和抗体识别。这种识别是特异性的，因为它可被重组HIV-1 gp120阻断。此外，这些V3单克隆抗体以及识别这些V3样蛋白的艾滋病患者血清，可诱导HIV-1感染的以及未感染的T细胞死亡。HIV-1 gp120 V3肽也可抑制这种杀伤作用。这些结果表明，V3环与刺激的T细胞上的蛋白质共享表位。这可能是导致艾滋病中CD4+ T细胞消失的另一种自身免疫机制。V3抗体已被提议作为潜在的预防剂。然而，如果此类疫苗基于某些表位，它们可能会诱导与细胞蛋白的交叉反应性免疫应答。候选疫苗应评估此类潜在影响。
