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Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.


ABSTRACT: MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/class I transactivator. In this study, we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and related genes such as ?(2)-microglobulin, Tap1, or Lmp2, but did not affect MHC class II levels. IFN-? stimulation could not overcome the impaired MHC class I expression in Nlrc5-deficient cells. Upon infection with Listeria monocyogenes, Nlrc5-deficient mice displayed impaired CD8(+) T cell activation, accompanied with increased bacterial loads. These findings illustrate critical roles of NLRC5/class I transactivator in MHC class I gene regulation and host defense by CD8(+) T cell responses.

SUBMITTER: Biswas A 

PROVIDER: S-EPMC3578426 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.

Biswas Amlan A   Meissner Torsten B TB   Kawai Taro T   Kobayashi Koichi S KS  

Journal of immunology (Baltimore, Md. : 1950) 20120618 2


MHC class I and class II are crucial for the adaptive immune system. Although regulation of MHC class II expression by CIITA has long been recognized, the mechanism of MHC class I transactivation has been largely unknown until the recent discovery of NLRC5/class I transactivator. In this study, we show using Nlrc5-deficient mice that NLRC5 is required for both constitutive and inducible MHC class I expression. Loss of Nlrc5 resulted in severe reduction in the expression of MHC class I and relate  ...[more]

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