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首页> 外文期刊>Infection and immunity >Leishmania pifanoi Amastigote Antigen P-4: Epitopes Involved in T-Cell Responsiveness in Human Cutaneous Leishmaniasis
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Leishmania pifanoi Amastigote Antigen P-4: Epitopes Involved in T-Cell Responsiveness in Human Cutaneous Leishmaniasis

机译：利什曼原虫pifanoi鞭毛抗原P-4：涉及人类皮肤利什曼病的T细胞反应性的抗原决定簇。

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In experimental murine cutaneous leishmaniasis, the purifiedLeishmania pifanoi amastigote protein P-4 has been shown to induce significant protection against infection. Further, recent studies examining the response of peripheral blood mononuclear cells (PBMC) from Leishmania braziliensis-infected human patients have demonstrated that the P-4 protein selectively elicits a significant TH1-like response. Because a TH1-like response is associated with cure, epitope studies were conducted to further evaluate the human response to P-4. PBMC from confirmed cutaneous leishmaniasis patients infected withL. braziliensis in Rio de Janeiro, Brazil, an area where the disease is endemic, were examined for T-cell proliferation and/or cytokine production in response to whole-parasite homogenate, isolated P-4 protein, and/or P-4 peptides. Twenty of the 22 patients (91%) examined responded to the native P-4 protein by proliferation and/or gamma interferon (IFN-γ) production. According to the proliferation data, PBMC from 14 patients (64%) were found to respond to the intact P-4 protein (stimulation index of ≥2.5). Fifty-seven percent of the P-4-responsive patients studied responded to at least one of the P-4 peptides; 11 individual peptides were found to elicit a proliferative response. Of 17 patients examined for cytokine production, no PBMC produced detectable interleukin-4 in response to P-4 protein or peptides. However, PBMC from 14 patients (82%) produced significant levels of IFN-γ (≥20 pg/ml) in response to native P-4 protein. Nineteen of the 23 peptides were found to elicit an IFN-γ response from at least two patients. These data indicate that multiple epitopes spanning the entire P-4 molecule are responsible for the TH1-like immune response observed, indicating that the intact P-4 amastigote molecule, rather than selected peptides, may prove to be the most useful for leishmaniasis vaccine development.
机译：在实验性小鼠皮肤利什曼病中，纯化的 Leishmania pifanoi 鞭毛体蛋白P-4已显示出对感染的显着保护作用。此外，最近研究检查来自巴西利什曼原虫感染的人类患者的外周血单个核细胞（PBMC）反应的研究表明，P-4蛋白选择性地引起了显着的T H 类似1的回应。由于类似T sub 1的反应与治愈相关，因此进行了表位研究以进一步评估人类对P-4的反应。确诊皮肤利什曼病患者感染emL的PBMC。检查了巴西里约热内卢该病流行地区的巴西巴西人对全寄生虫匀浆，分离的P-4蛋白和/或P的反应性T细胞增殖和/或细胞因子产生-4肽。检查的22例患者中有20例（91％）通过增殖和/或产生γ-干扰素（IFN-γ）对天然P-4蛋白有反应。根据增殖数据，发现14例患者的PBMC（64％）对完整的P-4蛋白有反应（刺激指数≥2.5）。在接受研究的P-4反应患者中，有57％对至少一种P-4肽有反应;发现11种单独的肽引起增殖反应。在检查的17位细胞因子产生患者中，没有PBMC响应P-4蛋白或肽产生可检测到的白介素4。但是，来自14位患者（82％）的PBMC对天然P-4蛋白产生了显着水平的IFN-γ（≥20pg / ml）。发现这23种肽中有19种会引起至少两名患者的IFN-γ反应。这些数据表明，跨越整个P-4分子的多个表位是所观察到的T H -1免疫反应的原因，表明完整的P-4鞭毛体分子而不是选定的肽可能证明对利什曼病疫苗的开发最有用。

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