Pérarnau B, Saron M F, Reina San Martin B, Bervas N, Ong H, Soloski M J, Smith A G, Ure J M, Gairin J E, Lemonnier F A
Département SIDA-Rétrovirus, Institut Pasteur, Paris, France.
Eur J Immunol. 1999 Apr;29(4):1243-52. doi: 10.1002/(SICI)1521-4141(199904)29:04<1243::AID-IMMU1243>3.0.CO;2-A.
Single H2Kb, H2Db and double H2KbDb homozygous knockout (KO) mice were generated and their peripheral CD8+ T cell repertoires compared to that of C57BL/6 (B6) mice. Limited (10-20%, H2Db), substantial (30-50%, H2Kb) and profound (90%, H2KbDb) reduction of peripheral CD8+ T cells was observed in KO mice, without Vbeta diversity alteration. Classical class Ia molecules therefore ensure most but not all of the peripheral CD8+ T cell repertoire education. As expected, H2Kb but also H2Db KO mice developed choriomeningitis following intracranial infection by lymphocytic choriomeningitis virus with the same kinetics, lethality and CD8+ cell implication as wild-type B6 mice. By contrast, H2KbDb (class Ia-Ib+) KO mice survived. Choriomeningitis of H2Db KO mice was linked to the development of a subdominant (in normal B6 mice) H2Kb-restricted cytotoxic T lymphocyte response. Mice expressing a restricted set of histocompatibility class I molecules should represent useful tools to evaluate the immunological potentials of individual MHC class I molecules.
生成了单H2Kb、H2Db以及双H2KbDb纯合敲除（KO）小鼠，并将它们的外周CD8+T细胞库与C57BL/6（B6）小鼠的进行比较。在敲除小鼠中观察到外周CD8+T细胞有限（10 - 20%，H2Db）、显著（30 - 50%，H2Kb）和深度（90%，H2KbDb）减少，而Vβ多样性未改变。因此，经典的I类分子确保了大部分但并非所有外周CD8+T细胞库的发育。正如预期的那样，H2Kb以及H2Db敲除小鼠在受到淋巴细胞性脉络丛脑膜炎病毒颅内感染后，出现脉络丛脑膜炎，其动力学、致死率和CD8+细胞参与情况与野生型B6小鼠相同。相比之下，H2KbDb（I类 - Ib+）敲除小鼠存活下来。H2Db敲除小鼠的脉络丛脑膜炎与一种在正常B6小鼠中占次要地位的H2Kb限制性细胞毒性T淋巴细胞反应的发展有关。表达一组有限的组织相容性I类分子的小鼠应是评估单个MHC I类分子免疫潜力的有用工具。
