Romero P, Maryanski J L, Corradin G, Nussenzweig R S, Nussenzweig V, Zavala F
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York 10016.
Nature. 1989 Sep 28;341(6240):323-6. doi: 10.1038/341323a0.
Protective immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly against the repeat domain of the circumsporozoite protein. Early experiments showed, however, that B-cell-depleted mice that are immunized with sporozoites can resist challenge, indicating that T-cell effector mechanisms may also have a role in protection. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CD8 antigen (CD8+ T cells) whose target is probably the developing liver-stage parasites. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies. Here we report the identification of an epitope contained within amino acids 249-260 of the Plasmodium berghei circumsporozoite protein that is recognized by H-2Kd-restricted cytotoxic T cells. Passive transfer into mice of cytotoxic-T-cell clones that recognize this epitope conferred a high degree of protection against challenge. These results provide the first direct evidence that CD8+ T cells that are specific for a defined epitope can confer protection against a parasitic infection.
通过用经辐射减毒的子孢子对宿主进行疫苗接种可诱导针对疟疾的保护性免疫。这种免疫部分由中和抗体介导，这些抗体主要针对环子孢子蛋白的重复结构域。然而，早期实验表明，用子孢子免疫的B细胞缺失小鼠能够抵抗攻击，这表明T细胞效应机制可能在保护中也发挥作用。最近的观察结果支持了这一观点，即保护性免疫还需要表达CD8抗原的T细胞（CD8 + T细胞），其靶标可能是发育中的肝期寄生虫。此外，一种表达环子孢子蛋白的口服沙门氏菌疫苗在没有抗体的情况下能够预防小鼠疟疾。在这里，我们报告了对伯氏疟原虫环子孢子蛋白249 - 260氨基酸内所含表位的鉴定，该表位可被H - 2Kd限制的细胞毒性T细胞识别。将识别该表位的细胞毒性T细胞克隆被动转移到小鼠体内可提供高度的攻击保护。这些结果提供了首个直接证据，即针对特定表位的CD8 + T细胞可提供针对寄生虫感染的保护。
