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首页> 外文期刊>Infection and immunity >Reactivity profile of human anti-82-kilodalton rhoptry protein antibodies generated during natural infection with Plasmodium falciparum.
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Reactivity profile of human anti-82-kilodalton rhoptry protein antibodies generated during natural infection with Plasmodium falciparum.

机译：在恶性疟原虫自然感染过程中产生的人类抗82-千洛酮顿河蛋白抗体的反应性概况。

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Immunization of monkeys with the 82-kDa rhoptry protein (p82) of Plasmodium falciparum can protect them against a lethal blood stage challenge, and monoclonal antibodies to p82 inhibit parasite growth in vitro. The role that a p82-specific immune response might play in human immunity to the parasite is not known. To determine to what extent humans produce antibodies to p82 following infection with P. falciparum, sera from individuals believed to be hyperimmune, semi-immune, or never infected with the parasite were examined. Portions of the p82 gene were expressed separately as fusion proteins and used on immunoblots to test for antibodies to the recombinant proteins. All but 1 of the 30 immune sera possessed antibodies to p82, while nonimmune sera produced, at best, only a marginal signal to the fusion proteins. The signal intensity produced with the human immune sera depended on the region of p82 being assayed, with the N-terminal 37% of p82 producing stronger signals than more C-terminal parts of p82. This N-terminal domain contains a tandem octapeptide repeat (consensus KSSSPSXT/V) of the structure (repeat)2-Q-T-S-G-S/L-(repeat)3. It is shown here that the sequence of this repetitive motif is conserved among four parasite isolates at both the nucleotide and amino acid levels; the five-residue repeat interruption peptide QTSGS/L separating the two sets of repeats contains the only amino acid substitution (Ser or Leu) detected in this region to date. Despite their conservation of structure, the repeats do not appear to be the only epitope recognized by the human antibodies, since sera which recognize the N-terminal fusion protein containing the repeats also bind a related protein after truncation and removal of the repeats. These results indicate that the structurally conserved p82 molecule contains multiple B-cell epitopes and is likely to be immunogenic in most individuals during natural infections with P. falciparum. These observations are consistent with the idea that antibodies to p82 generated during parasite infection have a role in the development of immunity to the organism.
机译：用恶性疟原虫的82 kDa rhoptry蛋白（p82）免疫猴子可以保护它们免受致命的血液阶段攻击，p82的单克隆抗体可以在体外抑制寄生虫的生长。 p82特异性免疫反应在人类对寄生虫的免疫中可能发挥的作用尚不清楚。为了确定人类在恶性疟原虫感染后在多大程度上产生针对p82的抗体，检查了被认为是超免疫，半免疫或从未感染过该寄生虫的个体的血清。 p82基因的部分分别作为融合蛋白表达，并在免疫印迹中用于测试针对重组蛋白的抗体。在30个免疫血清中，除1个外，其他所有抗体都具有针对p82的抗体，而非免疫血清充其量仅对融合蛋白产生少量信号。人类免疫血清产生的信号强度取决于所分析的p82区域，p82的N端37％会比p82的C端更多地产生更强的信号。该N端结构域包含结构（重复）2 -Q-T-S-G-S / L-（重复）3的串联八肽重复序列（共有KSSSPSXT / V）。在此表明，该重复基序的序列在核苷酸和氨基酸水平上在四个寄生虫分离物中是保守的。分离两组重复序列的五残基重复序列中断肽QTSGS / L包含迄今为止在该区域中检测到的唯一氨基酸取代（Ser或Leu）。尽管保留了结构，但这些重复序列似乎不是人类抗体识别的唯一表位，因为识别包含重复序列的N端融合蛋白的血清在重复序列被切除和去除后也与相关蛋白结合。这些结果表明，结构保守的p82分子包含多个B细胞表位，在恶性疟原虫的自然感染过程中，大多数个体可能具有免疫原性。这些观察结果与寄生虫感染过程中产生的针对p82的抗体在对机体免疫力的发展中起作用有关。

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