Bouwer H G, Seaman M S, Forman J, Hinrichs D J
Immunology Research, Veterans Affairs Medical Center and Earle A. Chiles Research Institute, Portland, Oregon 97201, USA.
J Immunol. 1997 Sep 15;159(6):2795-801.
Subclinical infection of BALB/c mice with the intracellular pathogen Listeria monocytogenes results in the development of MHC class Ia- and Ib-restricted CTLs. L. monocytogenes-infected TAP-/- bone marrow macrophage targets are not lysed by MHC class Ia- or Ib-restricted CTLs, showing a requirement for transport of peptides into the endoplasmic reticulum for development of the MHC class Ib-peptide target. L. monocytogenes-infected B6.Tla(a)-derived bone marrow macrophages (Kb Qa-1a) are not lysed by BALB/c (Kd Qa-1b)-derived antilisterial CTLs, confirming an earlier finding that the Ib-restricting element is T region encoded. We have further determined that Qa-1b is a restricting element for antilisterial CTLs using L. monocytogenes-infected Qa-1b-transformed mouse L cells as well as human-derived HeLa cells as target populations. These L. monocytogenes-infected Qa-1b-transformed cell lines are lysed by BALB/c (Qa-1b)- or C57BL/6 (Qa-1b)-derived antilisterial CTLs, but are not lysed by B6.AKM (Qa-1a)-derived antilisterial CTLs. Using L. monocytogenes-infected targets, we found that MHC class Ia- and Ib-restricted CTLs are evident within 4 days following infection, peak on day 5 following infection, and although Ib-restricted CTLs disappear by day 6 postinfection, la-restricted antilisterial CTL activity can still be detected. These results demonstrate that Qa-1b is a restricting element for antilisterial CTLs, and expression of the MHC class Ib-presented target at the cell surface is TAP dependent. In addition, these results show that following L. monocytogenes infection, MHC class Ib-restricted CTLs are evident in vivo.
用细胞内病原体单核细胞增生李斯特菌对BALB/c小鼠进行亚临床感染，会导致MHC I类a型和I类b型限制性细胞毒性T淋巴细胞（CTL）的产生。单核细胞增生李斯特菌感染的TAP-/-骨髓巨噬细胞靶细胞不会被MHC I类a型或I类b型限制性CTL裂解，这表明肽转运到内质网对于MHC I类b型肽靶细胞的形成是必需的。单核细胞增生李斯特菌感染的B6.Tla(a)来源的骨髓巨噬细胞（Kb Qa-1a）不会被BALB/c（Kd Qa-1b）来源的抗李斯特菌CTL裂解，这证实了早期的发现，即I类b型限制性元件是由T区域编码的。我们进一步确定，使用单核细胞增生李斯特菌感染的Qa-1b转化的小鼠L细胞以及人源HeLa细胞作为靶细胞群体时，Qa-1b是抗李斯特菌CTL的限制性元件。这些单核细胞增生李斯特菌感染的Qa-1b转化细胞系会被BALB/c（Qa-1b）或C57BL/6（Qa-1b）来源的抗李斯特菌CTL裂解，但不会被B6.AKM（Qa-1a）来源的抗李斯特菌CTL裂解。使用单核细胞增生李斯特菌感染的靶细胞，我们发现MHC I类a型和I类b型限制性CTL在感染后4天内明显出现，在感染后第5天达到峰值，尽管I类b型限制性CTL在感染后第6天消失，但I类a型限制性抗李斯特菌CTL活性仍然可以检测到。这些结果表明，Qa-1b是抗李斯特菌CTL的限制性元件，并且MHC I类b型呈递的靶细胞在细胞表面的表达依赖于TAP。此外，这些结果表明，在单核细胞增生李斯特菌感染后，MHC I类b型限制性CTL在体内是明显存在的。
