Russo D M, Jardim A, Carvalho E M, Sleath P R, Armitage R J, Olafson R W, Reed S G
Seattle Biomedical Research Institute, WA 98109.
J Immunol. 1993 Feb 1;150(3):932-9.
Both a conserved surface metalloprotease of leishmania, gp63 as well as certain gp63-derived peptides, have been shown to have immunoprophylactic potential in mouse models of leishmaniasis. In addition, PBMC from individuals with cutaneous, mucosal, or cured visceral leishmaniasis respond in vitro to both native and rgp63. In this report, we mapped human T cell epitopes within gp63. T cells from leishmaniasis patients responded in vitro to certain peptides of gp63 by proliferation and IFN-gamma production. One peptide, (PT7), stimulated cells from all individuals tested (n = 7). Anti-PT7 T cell lines derived from PBMC of a mucosal leishmaniasis patient contained a heterogeneous population of cells which responded by proliferation and IFN-gamma production to in vitro stimulation with Leishmania promastigote lysate. Another peptide (PT1) derived from Leishmania chagasi gp63 stimulated PBMC from an L. chagasi patient although the corresponding Leishmania major-derived peptide did not. Both L. major PT7 and L. chagasi PT1 were able to induce anti-Leishmania-specific T cell lines from normal human PBMC. These T cell lines responded to in vitro stimulation with promastigote lysate indicating that both peptides were immunogenic for naive T cells in vitro. In conclusion, both antigenic and immunogenic gp63 peptide sequences have been defined, some appearing to be conserved among Leishmania species and at least one that appears to be species specific.
利什曼原虫的一种保守表面金属蛋白酶gp63以及某些gp63衍生肽，已在利什曼病小鼠模型中显示出免疫预防潜力。此外，来自皮肤型、黏膜型或已治愈内脏型利什曼病患者的外周血单核细胞（PBMC）在体外对天然和重组gp63均有反应。在本报告中，我们绘制了gp63内的人类T细胞表位。利什曼病患者的T细胞在体外通过增殖和产生γ干扰素对gp63的某些肽作出反应。一种肽（PT7）刺激了所有受试个体（n = 7）的细胞。从一名黏膜利什曼病患者的PBMC中获得的抗PT7 T细胞系包含异质性细胞群体，这些细胞通过增殖和产生γ干扰素对利什曼原虫前鞭毛体裂解物的体外刺激作出反应。另一种源自恰加斯利什曼原虫gp63的肽（PT1）刺激了一名恰加斯利什曼病患者的PBMC，而相应的大利什曼原虫衍生肽则无此作用。大利什曼原虫PT7和恰加斯利什曼原虫PT1均能够从正常人PBMC中诱导出抗利什曼原虫特异性T细胞系。这些T细胞系对前鞭毛体裂解物的体外刺激有反应，表明这两种肽在体外对未致敏T细胞具有免疫原性。总之，已确定了具有抗原性和免疫原性的gp63肽序列，其中一些序列在利什曼原虫物种之间似乎是保守的，至少有一个序列似乎具有物种特异性。
