T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules.
T cell responses to Gram-negative intracellular bacterial pathogens: a role for CD8+ T cells in immunity to Salmonella infection and the involvement of MHC class Ib molecules.
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DOI：
10.4049/jimmunol.162.9.5398
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发表时间：
1999-05
影响因子：
4.4
通讯作者：
W. Lo;H. Ong;E. Metcalf;M. Soloski
中科院分区：
文献类型：
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作者：
W. Lo;H. Ong;E. Metcalf;M. Soloski
尽管是细胞内病原体的一个主要类别，但I类限制性T细胞在清除革兰氏阴性菌中的作用尚未明确。利用鼠伤寒模型，揭示了I类限制性T细胞在对革兰氏阴性病原体鼠伤寒沙门氏菌的免疫应答中的作用。I类缺陷的β2 -微球蛋白基因敲除（β2 - microglobulin - / -）小鼠对鼠伤寒沙门氏菌感染的易感性增加。感染后，能够很容易地检测到针对沙门氏菌感染靶细胞的CD8 + 细胞毒性T淋巴细胞（CTL）。沙门氏菌特异性CTL能够识别感染的H - 2不匹配的靶细胞，这表明共享的Ib类分子参与其中。使用表达特定的Ia类和Ib类分子的转染细胞进行的研究表明Ib类分子Qa - 1参与其中。抗体阻断研究以及细菌特异性CTL频率的测定确定Qa - 1是一种主要的限制性元件。Qa - 1限制性CTL识别依赖于抗原加工相关转运体（TAP）和蛋白酶体功能。令人惊讶的是，Qa - 1限制性CTL能够识别被其他密切相关的革兰氏阴性菌感染的细胞。综上所述，这些观察结果表明沙门氏菌特异性CTL识别由Qa - 1分子呈递的交叉反应性表位，因此，可能是疫苗开发的新靶点。
Despite being a major group of intracellular pathogens, the role of class I-restricted T cells in the clearance of Gram-negative bacteria is not resolved. Using a murine typhoid model, a role for class I-restricted T cells in the immune response to the Gram-negative pathogen Salmonella typhimurium is revealed. Class I-deficient beta2-microglobulin-/- mice show increased susceptibility to infection with S. typhimurium. Following infection, CD8+ CTLs specific for Salmonella-infected targets can be readily detected. The Salmonella-specific CTLs recognize infected H-2-mismatched targets, suggesting the involvement of shared class Ib molecules. Studies using transfectants expressing defined class Ia and class Ib molecules indicate the involvement of the class Ib molecule, Qa-1. Ab-blocking studies and the measurement of bacteria-specific CTL frequencies identified Qa-1 as a dominant restricting element. The Qa-1-restricted CTL recognition depends on TAP and proteasome functions. Surprisingly, Qa-1-restricted CTLs recognized cells infected with other closely related Gram-negative bacteria. Taken together, these observations indicate that Salmonella-specific CTLs recognize a cross-reactive epitope presented by Qa-1 molecules and, as such, may be novel targets for vaccine development.