Pathak Sulabha, Rajeshwari K, Garg Swati, Rajagopal Sudarsan, Patel Kalpesh, Das Bidyut, Pied Sylviane, Ravindran Balachandran, Sharma Shobhona
Malarial Parasite Biology Laboratory, Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
J Biomed Biotechnol. 2012;2012:695843. doi: 10.1155/2012/695843. Epub 2012 Jan 17.
Passive immunization with antibodies to recombinant Plasmodium falciparum P0 riboprotein (rPfP0, 61-316 amino acids) provides protection against malaria. Carboxy-terminal 16 amino acids of the protein (PfP0C0) are conserved and show 69% identity to human and mouse P0. Antibodies to this domain are found in 10-15% of systemic lupus erythematosus patients. We probed the nature of humoral response to PfP0C0 by repeatedly immunizing mice with rPfP0. We failed to raise stable anti-PfP0C0 hybridomas from any of the 21 mice. The average serum anti-PfP0C0 titer remained low (5.1 ± 1.3 × 10⁴). Pathological changes were observed in the mice after seven boosts. Adsorption with dinitrophenyl hapten revealed that the anti-PfP0C0 response was largely polyreactive. This polyreactivity was distributed across all isotypes. Similar polyreactive responses to PfP0 and PfP0C0 were observed in sera from malaria patients. Our data suggests that PfP0 induces a deviant humoral response, and this may contribute to immune evasion mechanisms of the parasite.
用针对重组恶性疟原虫P0核糖蛋白(rPfP0,61 - 316个氨基酸)的抗体进行被动免疫可提供抗疟疾保护。该蛋白的羧基末端16个氨基酸(PfP0C0)是保守的,与人和小鼠的P0有69%的同一性。在10% - 15%的系统性红斑狼疮患者中发现了针对该结构域的抗体。我们通过用rPfP0反复免疫小鼠来探究对PfP0C0的体液反应的性质。我们未能从21只小鼠中的任何一只培育出稳定的抗PfP0C0杂交瘤。血清抗PfP0C0平均滴度仍然很低(5.1 ± 1.3 × 10⁴)。在七次加强免疫后,小鼠出现了病理变化。用二硝基苯基半抗原吸附表明,抗PfP0C0反应在很大程度上是多反应性的。这种多反应性分布在所有同种型中。在疟疾患者的血清中也观察到了对PfP0和PfP0C0类似的多反应性反应。我们的数据表明,PfP0诱导了一种异常的体液反应,这可能有助于寄生虫的免疫逃逸机制。