Basu Rajatava, Roy Syamal, Walden Peter
Clinical Research Group, Department of Dermatology, Venerology and Allergology, Charite-Universitatsmedizin Berlin, Humboldt University, Berlin, D-10117, Germany.
J Infect Dis. 2007 May 1;195(9):1373-80. doi: 10.1086/513439. Epub 2007 Mar 20.
Visceral leishmaniasis is a protozoal disease caused by the intracellular parasites Leishmania donovani and L. chagasi/infantum, and it is usually deadly if not treated. To date, no vaccine exists for prophylaxis or immunotherapy, nor has it been established which effector mechanisms of the immune system are most instrumental against the parasites. Recent reports have suggested that CD8(+) T cells, in addition to CD4(+) T cells, might play major roles in the defense against infection and in the cure of the disease. To identify epitopes recognized by CD8(+) T cells that can be used for immune monitoring to investigate the role of these cells in human visceral leishmaniasis, as well as in vaccine development, we scanned the entire sequence of the leishmanial protein kinetoplastid membrane protein (kmp)-11 with overlapping nonapeptides. Thirty peptides that specifically trigger interferon- gamma secretion by human CD8(+) T cells were identified. Four T cell lines with specificities for different peptides recognize Leishmania-infected autologous macrophages, which proves that kmp-11 is processed and presented via the major histocompatibility complex class I pathway of infected cells. Kmp-11 is thus a candidate antigen for the development of T cell vaccines.
内脏利什曼病是一种由细胞内寄生虫杜氏利什曼原虫和恰加斯利什曼原虫/婴儿利什曼原虫引起的原生动物疾病，若不治疗通常会致命。迄今为止，尚无用于预防或免疫治疗的疫苗，免疫系统的哪些效应机制对寄生虫最具作用也尚未明确。最近的报告表明，除了CD4(+) T细胞外，CD8(+) T细胞可能在抵御感染和治愈疾病中发挥主要作用。为了鉴定可被CD8(+) T细胞识别的表位，用于免疫监测以研究这些细胞在人类内脏利什曼病中的作用以及在疫苗开发中的作用，我们用重叠九肽扫描了利什曼原虫蛋白动质体膜蛋白（kmp）-11的整个序列。鉴定出了30种能特异性触发人类CD8(+) T细胞分泌干扰素-γ的肽。四种对不同肽具有特异性的T细胞系可识别感染利什曼原虫的自体巨噬细胞，这证明kmp-11是通过受感染细胞的主要组织相容性复合体I类途径加工和呈递的。因此，kmp-11是开发T细胞疫苗的候选抗原。
