Knight S C, Iqball S, Woods C, Stagg A, Ward M E, Tuffrey M
St. Mary's Hospital Medical School, Northwick Park Hospital, Harrow, UK.
Immunology. 1995 May;85(1):8-15.
Chlamydiae are a major cause of infertility and preventable blindness and there is currently no effective vaccine in humans or rodents against these organisms. We have previously shown that a peptide of 12 amino acids (termed TINKP) from a conserved region of the major outer membrane protein (MOMP) of Chlamydia trachomatis (C. trachomatis) is a primary T-cell epitope in humans. Here we showed that when dendritic cells (DC) from C3H or BALB/c mice were pulsed in vitro with the peptide they stimulated proliferation of syngeneic T cells in vitro indicating that the peptide is also a primary T-cell epitope in mice. Since the skin is a rich source of DC, we immunized mice from each strain with an intradermal injection of the peptide. Humoral and cell-mediated immunity to peptide, MOMP or whole elementary bodies (EB) of C. trachomatis (F/NI1/GU) were assessed. No antibody response to TINKP was observed. However, immunized mice showed recall responses to all three chlamydial antigens. T-cell-mediated immunity in the absence of antibody was induced by a single injection of the peptide intradermally. C. trachomatis isolated from the human genital tract causes salpingitis in mice. Preliminary studies in susceptible C3H mice indicated that intradermal injection of peptide conferred some protection against the development of salpingitis. Thus, a primary T-cell epitope identified by in vitro stimulation using DC can also initiate cell-mediated immunity in vivo and this approach may be useful in the development of vaccines.
衣原体是导致不孕不育和可预防失明的主要原因,目前在人类或啮齿动物中尚无针对这些病原体的有效疫苗。我们之前已经表明,沙眼衣原体主要外膜蛋白(MOMP)保守区域的一个12氨基酸肽(称为TINKP)是人类的主要T细胞表位。在此我们表明,当用该肽体外脉冲处理C3H或BALB/c小鼠的树突状细胞(DC)时,它们能在体外刺激同基因T细胞增殖,这表明该肽在小鼠中也是主要T细胞表位。由于皮肤是DC的丰富来源,我们对每个品系的小鼠进行皮内注射该肽免疫。评估了对该肽、MOMP或沙眼衣原体(F/NI1/GU)全原体(EB)的体液免疫和细胞介导免疫。未观察到对TINKP的抗体反应。然而,免疫小鼠对所有三种衣原体抗原均表现出回忆反应。通过皮内单次注射该肽可诱导无抗体情况下的T细胞介导免疫。从人类生殖道分离出的沙眼衣原体可在小鼠中引起输卵管炎。对易感C3H小鼠的初步研究表明,皮内注射该肽可对输卵管炎的发展提供一定保护。因此,通过使用DC体外刺激鉴定出的主要T细胞表位也可在体内启动细胞介导免疫,这种方法可能对疫苗开发有用。