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人原代T细胞对沙眼衣原体主要外膜蛋白的反应。

Primary human T-cell responses to the major outer membrane protein of Chlamydia trachomatis.

作者信息

Stagg A J, Elsley W A, Pickett M A, Ward M E, Knight S C

机构信息

Antigen Presentation Research Group, Clinical Research Centre, Harrow, Middlesex, U.K.

出版信息

Immunology. 1993 May;79(1):1-9.

Abstract

The major outer membrane protein (MOMP) of Chlamydia trachomatis is the main candidate antigen for a synthetic vaccine against chlamydial infection. Antibodies to surface-exposed epitopes on MOMP neutralize chlamydial infectivity but little is known about T-cell recognition of the molecule. We have measured primary human T-cell responses to recombinant fragments of MOMP as well as to the whole organism and synthetic MOMP peptides. Using antigen-pulsed low density cells (LDC) we were able to stimulate proliferative responses with T cells from most naive individuals. This response was antigen dose dependent and displayed an absolute requirement for dendritic cells in the antigen-presenting cell (APC) population. Several T-cell epitopes were identified in MOMP and one which stimulated T cells from 80% of donors was resolved as a 12 amino acid synthetic peptide. Dual cell surface labelling and cell cycle analysis by FACS revealed that both CD4+ and CD8+ T cells were stimulated in these cultures. The fact that we were able to obtain proliferative responses and interferon-gamma (IFN-gamma) production to MOMP using cells from cord bloods confirmed that these are genuine primary responses. These experiments have identified a region on MOMP, to which T cells from most humans make a primary response, which may be useful in a chlamydial vaccine. The approach is useful for vaccine development in general.

摘要

沙眼衣原体主要外膜蛋白(MOMP)是抗衣原体感染合成疫苗的主要候选抗原。针对MOMP表面暴露表位的抗体可中和衣原体感染性,但对于该分子的T细胞识别了解甚少。我们检测了原代人T细胞对MOMP重组片段、完整生物体及合成MOMP肽段的反应。使用抗原脉冲低密度细胞(LDC),我们能够刺激大多数未接触过抗原个体的T细胞产生增殖反应。这种反应呈抗原剂量依赖性,且在抗原呈递细胞(APC)群体中对树突状细胞有绝对需求。在MOMP中鉴定出了多个T细胞表位,其中一个能刺激80%供体的T细胞,该表位被解析为一个12氨基酸的合成肽段。通过荧光激活细胞分选术(FACS)进行的双细胞表面标记和细胞周期分析表明,在这些培养物中CD4⁺和CD8⁺ T细胞均受到刺激。我们能够使用脐血中的细胞获得针对MOMP的增殖反应和干扰素-γ(IFN-γ)产生,这一事实证实了这些是真正的原代反应。这些实验确定了MOMP上的一个区域,大多数人的T细胞对该区域产生原代反应,这可能对衣原体疫苗有用。该方法总体上对疫苗开发很有用。

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