Del Giudice G, Cheng Q, Mazier D, Berbiguier N, Cooper J A, Engers H D, Chizzolini C, Verdini A S, Bonelli F, Pessi A
Department of Pathology, University of Geneva, Switzerland.
Immunology. 1988 Feb;63(2):187-91.
In the present work, the hypothesis that individuals naturally exposed to Plasmodium falciparum malaria infection in endemic areas produce antibodies directed against non-repetitive epitopes of the circumsporozoite protein was investigated. Using a synthetic peptide reproducing the non-repetitive group-conserved region I sequence, we have shown that specific anti-region I antibodies are detectable in sera from endemic countries. Of these sera, 87% also had antibodies against the immunodominant repetitive epitope (Asn-Ala-Asn-Pro, NANP) of P. falciparum. In order to study the immunogenicity of this non-repetitive epitope, a synthetic peptide consisting of both region I and three (NANP) repeats [RI-(NANP)3] was used to immunize inbred strains of mice. H-2b mice produced antibodies against both the repetitive and the non-repetitive epitope. These antibodies were specific for each epitope, recognized P. falciparum sporozoites in immunofluorescence, and inhibited sporozoite penetration into human liver cells in vitro. Non-H-2b mice were completely unresponsive. Lymph node cells from H-2b mice immunized with RI-(NANP)3 peptide proliferated in the presence of RI-(NANP)3 and of (NANP)4 peptide, but never in the presence of RI peptide alone. These findings demonstrate that in the configuration used (i) the non-repetitive epitope region I does not carry T-helper epitopes; (ii) the (NANP) repetitive epitope may act as a carrier for the immune response to region I in mice; and (iii) therefore, immune response to region I in man probably depends on the recognition of T-cell epitopes similar to those involved in the anti-NANP response: i.e. such a T epitope may be NANP itself in responding individuals or another, not yet recognized, sporozoite T-cell epitope.
在本研究中，我们调查了一个假说，即在疟疾流行地区自然暴露于恶性疟原虫感染的个体是否会产生针对环子孢子蛋白非重复表位的抗体。我们使用了一种合成肽来重现非重复的组保守区域I序列，结果表明，在来自流行国家的血清中可以检测到特异性的抗区域I抗体。在这些血清中，87%的血清还含有针对恶性疟原虫免疫显性重复表位（天冬酰胺-丙氨酸-天冬酰胺-脯氨酸，NANP）的抗体。为了研究这种非重复表位的免疫原性，我们使用了一种由区域I和三个（NANP）重复序列组成的合成肽[RI-(NANP)3]来免疫近交系小鼠。H-2b小鼠产生了针对重复表位和非重复表位的抗体。这些抗体对每个表位都具有特异性，在免疫荧光实验中能够识别恶性疟原虫子孢子，并在体外抑制子孢子侵入人肝细胞。非H-2b小鼠则完全没有反应。用RI-(NANP)3肽免疫的H-2b小鼠的淋巴结细胞在RI-(NANP)3和（NANP）4肽存在的情况下会增殖，但在仅存在RI肽的情况下则不会增殖。这些发现表明，在所使用的构型中：（i）非重复表位区域I不携带T辅助表位；（ii）（NANP）重复表位可能作为小鼠对区域I免疫反应的载体；（iii）因此，人类对区域I的免疫反应可能取决于对与抗NANP反应中所涉及的类似T细胞表位的识别：即这种T表位在有反应的个体中可能是NANP本身，或者是另一种尚未被识别的子孢子T细胞表位。
