Yang D M, Rogers M V, Liew F Y
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, Kent, U.K.
Immunology. 1991 Jan;72(1):3-9.
By using a series of overlapping synthetic peptides that cover more than 75% of the amino acid sequence of the major surface glycoprotein (gp63) from Leishmania major, 11 T-cell epitopes in CBA and BALB/c mice have been identified. Six of the peptides were recognized by T cells of CBA mice recovered from L. major infection, while one was recognized by the T cells from BALB/c mice recovered from the infection following sublethal doses of gamma-irradiation. Lymph node cells from mice immunized with the peptides also responded to a number of the same peptides (seven in CBA and one in BALB/c). Peptide p10-28 induced proliferative T-cell responses in both CBA and BALB/c mice. Five of the peptides (p10-28, p22-40, p289-309, p459-471 and p467-482) induced vigorous T-cell response in CBA mice but were not recognized by T cells from recovered mice. Four other peptides (p321-336, p364-476, p372-385 and p378-396) were recognized by T cells from recovered CBA mice but could not induce a T-cell response in normal CBA mice. Three peptides (p146-171, p289-309 and p395-414) were both able to induce a T-cell response and were recognized by T cells from recovered mice. However, only two peptides (p146-171 and p467-482) were able to activate T cells, which also recognized epitopes expressed by antigen-presenting cells infected with promastigotes. T cells induced by p146-171 and p467-171 or a mixture of these two peptides were mainly CD4+ and produced interleukin (IL-2) and interferon-gamma (IFN-gamma) but not IL-4 upon antigen stimulation in vitro. These two peptides also induced a classical delayed type hypersensitivity (DTH) response in CBA mice. Furthermore, CBA mice immunized with a mixture of the two peptides in Coryne parvum or entrapped in liposomes induced significant resistance against L. major infection. The implications of these results in terms of a synthetic vaccine against leishmaniasis and the mechanism of the induction of Th1 and Th2 cells are discussed.
通过使用一系列覆盖来自硕大利什曼原虫主要表面糖蛋白（gp63）超过75%氨基酸序列的重叠合成肽，已在CBA和BALB/c小鼠中鉴定出11个T细胞表位。其中6个肽被从硕大利什曼原虫感染中恢复的CBA小鼠的T细胞识别，而1个肽被经亚致死剂量γ射线照射后从感染中恢复的BALB/c小鼠的T细胞识别。用这些肽免疫的小鼠的淋巴结细胞也对许多相同的肽产生反应（CBA小鼠中有7个，BALB/c小鼠中有1个）。肽p10 - 28在CBA和BALB/c小鼠中均诱导了增殖性T细胞反应。其中5个肽（p10 - 28、p22 - 40、p289 - 309、p459 - 471和p467 - 482）在CBA小鼠中诱导了强烈的T细胞反应，但未被恢复小鼠的T细胞识别。另外4个肽（p321 - 336、p364 - 476、p372 - 385和p378 - 396）被从感染中恢复的CBA小鼠的T细胞识别，但在正常CBA小鼠中不能诱导T细胞反应。3个肽（p146 - 171、p289 - 309和p395 - 414）既能诱导T细胞反应，又能被恢复小鼠的T细胞识别。然而，只有2个肽（p146 - 171和p467 - 482）能够激活T细胞，这些T细胞也识别被前鞭毛体感染的抗原呈递细胞所表达的表位。由p146 - 171和p467 - 171或这两种肽的混合物诱导的T细胞主要是CD4 + ，在体外抗原刺激下产生白细胞介素（IL - 2）和干扰素 - γ（IFN - γ），但不产生IL - 4。这两种肽在CBA小鼠中也诱导了典型的迟发型超敏反应（DTH）。此外，用这两种肽的混合物在短小棒状杆菌中或包裹在脂质体中免疫的CBA小鼠对硕大利什曼原虫感染产生了显著的抵抗力。讨论了这些结果对于抗利什曼病合成疫苗的意义以及Th1和Th2细胞诱导机制。
