CONSTRUCTION OF PEPTIDES ENCOMPASSING MULTIDETERMINANT CLUSTERS OF HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE TO INDUCE INVITRO T-CELL RESPONSES IN MICE AND HUMANS OF MULTIPLE MHC TYPES
CONSTRUCTION OF PEPTIDES ENCOMPASSING MULTIDETERMINANT CLUSTERS OF HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE TO INDUCE INVITRO T-CELL RESPONSES IN MICE AND HUMANS OF MULTIPLE MHC TYPES
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DOI：
10.1172/jci115389
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发表时间：
1991-09-01
影响因子：
15.9
通讯作者：
SHEARER, GM
中科院分区：
文献类型：
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作者：
BERZOFSKY, JA;PENDLETON, CD;SHEARER, GM
为了使合成肽疫苗在广泛的远系繁殖人群中有效，必须掺入足够的抗原决定簇以引起大多数HLA类型的T细胞的识别。我们先前已经定义了人类免疫缺陷病毒（HIV）包膜的多决定簇区域，其中包括三种或四种单倍型小鼠增殖T细胞所见的重叠决定簇。我们现在已经验证了这样的假设，即包含这种多决定簇区域的合成肽将被多种鼠MHC类型的T细胞以及代表多种HLA类型的人T细胞识别。制备了6种长度为20-33个残基的这样的肽，并测试了它们刺激来自用重组包膜蛋白rgp 160免疫的4种不同MHC类型的小鼠以及来自42名不同HLA类型的HIV感染者的T细胞的能力。结果鉴定了几种这样的肽，它们被四种H-2型小鼠和52-73%的感染者广泛识别，这些感染者仍然保留IL-2产生性应答以控制回忆抗原，如甲型流感病毒或破伤风类毒素。针对至少三种肽测试的86%的这种感染的供体响应于六种肽中的至少一种，并且77%的另外的血清阳性组响应于肽的混合物。此外，所述肽可用于免疫小鼠以引发与完整的HIV包膜蛋白反应的T细胞。因此，这些肽可用于广泛人群中的疫苗开发以及诊断或预后用途。
To make synthetic peptide vaccines effective in a broad population of outbred humans, one would have to incorporate enough antigenic determinants to elicit recognition by T cells of most HLA types. We have previously defined multideterminant regions of the human immunodeficiency virus (HIV) envelope that include overlapping determinants seen by proliferating T cells of three or four haplotypes of mice. We have now tested the hypothesis that synthetic peptides encompassing such multideterminant regions will be recognized by T cells of multiple murine MHC types as well as by human T cells representing multiple HLA types. Six such peptides of 20-33 residues in length were prepared, and tested for their ability to stimulate T cells from mice of four distinct MHC types immunized with recombinant envelope protein rgp160, as well as from 42 HIV-infected humans of different HLA types. Results identify several such peptides that are broadly recognized by mice of four H-2 types and by 52-73% of infected humans who still retain IL-2 productive responses to control recall antigens such as influenza A virus or tetanus toxoid. 86% of such infected donors tested against at least three peptides respond to at least one of the six peptides, and 77% of an additional group of seropositives respond to a mixture of the peptides. Moreover, the peptides can be used to immunize mice to elicit T cells reactive with the intact HIV envelope protein. These peptides therefore may be useful for both vaccine development in the broad human population, and diagnostic or prognostic use.