Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania
Cytotoxic T lymphocytes to Plasmodium falciparum epitopes in an area of intense and perennial transmission in Tanzania
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DOI：
10.1002/eji.1830260408
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发表时间：
1996-04-01
影响因子：
5.4
通讯作者：
Hill, AVS
中科院分区：
文献类型：
--
作者：
Lalvani, A;Hurt, N;Hill, AVS
在冈比亚的研究提供了间接的证据，细胞毒性T淋巴细胞（CTL）发挥保护作用，对疟疾的人，最近，使用等位基因特异性HLA I类肽基序，几个肽表位的CTL在四个前红细胞恶性疟原虫抗原已被确定在自然暴露的冈比亚人。然而，CTL水平较低，这表明通过免疫增强这些低水平可能提供实质性保护。在坦桑尼亚的基隆贝罗山谷，疟疾传播是完全地方性的，比冈比亚的传播强度高300倍。我们在这里报告说，在冈比亚确定的几个表位也认识到在自然暴露，部分免疫坦桑尼亚成年人和CTL水平相似或略高于冈比亚的主题，尽管接种率高得多。我们报告了一个新的HLA-A2.1限制性表位从血小板反应蛋白相关的匿名蛋白（TRAP），我们证明，肽表位在TRAP的天然加工识别的CTL从自然暴露的人。环子孢子蛋白中可变HLA-B7限制性表位的共同等位基因表现为相对于该表位的罕见等位基因变体的CTL同源物的改变的肽配体（APL），这表明APL拮抗作用可能发生在对恶性疟原虫的天然CTL应答中。观察到的中等水平的CTL，即使在这一地区的疟疾传播密集，指出需要评估候选疫苗，旨在提高CTL水平。
Studies in The Gambia have provided indirect evidence that cytotoxic T lymphocytes (CTL) play a protective role against malaria in humans and recently, using allele-specific HLA class I peptide motifs, several peptide epitopes for CTL in four pre-erythrocytic Plasmodium falciparum antigens have been identified in naturally exposed Gambians. However, CTL levels were low, suggesting that boosting these low levels by immunization might provide substantial protection. In the Kilombero valley of Tanzania, malaria transmission is holoendemic and 300 times more intense than in The Gambia. We report here that several of the epitopes identified in The Gambia are also recognized in naturally exposed, partially immune Tanzanian adults and that levels of CTL are similar to or slightly higher than in Gambian subjects, despite the much higher inoculation rate. We report a new HLA-A2.1-restricted epitope from the thrombospondin-related anonymous protein (TRAP) and we demonstrate that peptide epitopes in TRAP are naturally processed for recognition by CTL from naturally exposed humans. The common allele of a variable HLA-B7-restricted epitope in the circumsporozoite protein behaved as an altered peptide ligand (APL) with respect to CTL cognate for a rarer allelic variant of this epitope, suggesting that APL antagonism may occur in natural CTL responses to P. falciparum. The moderate levels of CTL observed, even in this area of intense malaria transmission, points to the need to assess candidate vaccines aimed at increasing CTL levels.