Sinigaglia F, Guttinger M, Kilgus J, Doran D M, Matile H, Etlinger H, Trzeciak A, Gillessen D, Pink J R
Central Research Units, F. Hoffmann-La Roche & Co. Ltd, Basel, Switzerland.
Nature. 1988;336(6201):778-80. doi: 10.1038/336778a0.
An ideal vaccine should elicit a long lasting immune response against the natural parasite, both at the T- and B-cell level. The immune response should occur in all individuals and be directed against determinants that do not vary in the natural parasite population. A major problem in designing synthetic peptide vaccines is that T cells generally recognize peptide antigens only in association with one or a few of the many variants of major histocompatibility complex (MHC) antigens. During the characterization of epitopes of the malaria parasite Plasmodium falciparum that are recognized by human T cells, we analysed a sequence of the circumsporozoite protein, and found that synthetic peptides corresponding to this sequence are recognized by T cells in association with many different MHC class II molecules, both in mouse and in man. This region of the circumsporozoite protein is invariant in different parasite isolates. Peptides derived from this region should be capable of inducing T-cell responses in individuals of most HLA-DR types, and may represent good candidates for inclusion in an effective anti-malaria peptide vaccine.
理想的疫苗应在T细胞和B细胞水平上引发针对天然寄生虫的持久免疫反应。这种免疫反应应在所有个体中发生，并针对天然寄生虫群体中不变的决定簇。设计合成肽疫苗的一个主要问题是，T细胞通常仅在与主要组织相容性复合体（MHC）抗原的众多变体中的一种或几种相关联时才识别肽抗原。在对人类T细胞识别的疟原虫恶性疟原虫表位进行表征的过程中，我们分析了环子孢子蛋白的一个序列，发现与该序列相对应的合成肽在小鼠和人类中均能与许多不同的MHC II类分子相关联而被T细胞识别。环子孢子蛋白的这一区域在不同的寄生虫分离株中是不变的。源自该区域的肽应该能够在大多数HLA-DR类型的个体中诱导T细胞反应，并且可能是纳入有效抗疟疾肽疫苗的良好候选物。
