Cutting edge: impaired MHC class I expression in mice deficient for Nlrc5/class I transactivator.
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 β(2)-microglobulin, Tap1, or Lmp2, but did not affect MHC class II levels. IFN-γ 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.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Amlan
A
Biswas
Torsten B
TB
Meissner
Taro
T
Kawai
Koichi S
KS
Kobayashi
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C549161:NLRC5 protein, mouse; D015534:Trans-Activators