Lalvani A, Hurt N, Aidoo M, Kibatala P, Tanner M, Hill A V
Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, GB.
Eur J Immunol. 1996 Apr;26(4):773-9. doi: 10.1002/eji.1830260408.
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.
在冈比亚进行的研究提供了间接证据，表明细胞毒性T淋巴细胞（CTL）在人类抵抗疟疾中发挥保护作用。最近，利用等位基因特异性HLA I类肽基序，在自然暴露的冈比亚人中已鉴定出四种恶性疟原虫前红细胞期抗原中CTL的几个肽表位。然而，CTL水平较低，这表明通过免疫增强这些低水平可能会提供实质性的保护。在坦桑尼亚的基洛姆贝罗山谷，疟疾传播呈高度地方性流行，强度比冈比亚高300倍。我们在此报告，在冈比亚鉴定出的几个表位在自然暴露的、部分免疫的坦桑尼亚成年人中也能被识别，并且尽管接种率高得多，但CTL水平与冈比亚受试者相似或略高。我们报告了一种来自血小板反应蛋白相关匿名蛋白（TRAP）的新的HLA - A2.1限制性表位，并且我们证明TRAP中的肽表位在自然暴露的人类中能被自然加工以供CTL识别。环子孢子蛋白中一个可变的HLA - B7限制性表位的常见等位基因相对于该表位的一种罕见等位基因变体的CTL同源物表现为一种改变的肽配体（APL），这表明在对恶性疟原虫的天然CTL反应中可能发生APL拮抗作用。即使在这个疟疾传播强烈的地区观察到的CTL适度水平，也表明需要评估旨在提高CTL水平的候选疫苗。
