Peptide mimicry of carbohydrate epitopes on human immunodeficiency virus
Peptide mimicry of carbohydrate epitopes on human immunodeficiency virus
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DOI：
10.1038/nbt0697-547
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发表时间：
1997-06-01
影响因子：
46.9
通讯作者：
KieberEmmons, T
中科院分区：
文献类型：
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作者：
Agadjanyan, M;Luo, P;KieberEmmons, T
癌症相关的黏液型碳水化合物表位，主要是甘露糖和唾液基残基，在人类免疫缺陷病毒（HIV）的包膜蛋白gp160上表达，针对这些和其他碳水化合物表位的抗碳水化合物抗体已知可以中和无细胞病毒感染的HIV-1，然而，碳水化合物是T细胞非依赖性抗原，通常会引起免疫反应减弱。为了克服这种潜在的缺陷，我们研究了模拟这些表位的肽引发与碳水化合物结构交叉反应的免疫反应的能力，我们报告了针对模拟黏液相关碳水化合物表位的肽产生的小鼠多克隆抗血清具有抗hiv -1活性。抗体的产生不受ir基因的限制，因为至少有两种不同的小鼠菌株Balb/c （H-2(d)）和C57BI/6 （H-2(b)）对肽有相同的反应，抗肽血清对HIV-I/MN和HIV-I/3B病毒株表现出中和活性，这种中和效果与人类抗hiv血清一样好。这些结果表明，碳水化合物的肽模拟物为进一步开发试剂提供了一种新的策略，这些试剂可以引发与许多感染性生物和肿瘤细胞相关的碳水化合物表位的免疫反应。
Cancer-related, mucin-type carbohydrate epitopes, principally mannose and sialo-syl residues, are expressed on the envelope protein gp160 of the human immunodeficiency virus (HIV), Anticarbohydrate antibodies directed toward these and other carbohydrate epitopes are known to neutralize HIV-1 infection by cell-free virus, Carbohydrates, however, being T cell-independent antigens, typically elicit diminished immune responses. To overcome this potential draw back, we have examined the ability of peptides that mimic such epitopes to elicit immune responses that cross-react with carbohydrate structures, We report that mouse polyclonal antisera generated against peptides that mimic mucin-related carbohydrate epitopes have anti-HIV-1 activity. Generation of antibodies was not Ir-gene restricted, as at least two different strains of mice, Balb/c (H-2(d)) and C57BI/6 (H-2(b)), responded equally to the peptides, The antipeptide sera displayed neutralizing activity against HIV-I/MN and HIV-I/3B viral strains, This neutralization was as good as human anti-HIV sera. These results indicate that peptide mimics of carbohydrates provide a novel strategy for the further development of reagents that elicit immune responses to carbohydrate epitopes associated with many infectious organisms and tumor cells.