Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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Outline of Final Research Achievements |
pMHC II are continuously replaced with newly generated pMHC II through continuous ubiquitination by MARCH-I. The recycling of pMHC II is thought to be necessary for quick immune response against newly invading pathogens. In contrast, infectious stimuli inhibit recycling of pMHC II through inhibition of MARCH-I-mediated ubiquitination,thereby initiating immunity. Therefore, we are challenging to have experimental evidence for the hypotheses. We have generated the mice whose pMHC II is continuously ubiquitinated. This mouse showed impairment of immune response. In addition, the number of lymphocyte was reduced in the periphery. In MHC II-deficient mice, the number of leukocyte including lymphocyte was increased in the periphery, indicating that reduction of lymphocyte number is not simply due to down-regulation of MHC II in this mouse. Our results support the present hypothesis and suggest that regulated ubiquitination of pMHC II requires homeostasis of lymphocytes.
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