4.7 Article

Proteolysis of NF-kappa B1 p105 is essential for T cell antigen receptor-induced proliferation

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NATURE IMMUNOLOGY
卷 10, 期 1, 页码 38-47

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NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1685

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  1. UK Medical Research Council
  2. Medical Research Council [MC_U117573801, MC_U117527252, U117532003] Funding Source: researchfish
  3. MRC [MC_U117573801, MC_U117527252] Funding Source: UKRI

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To investigate the importance of proteolysis of NF-kappa B1 p105 induced by the kinase IKK in activation of the transcription factor NF-kappa B, we generated 'Nfkb1(SSAA/SSAA)' mice, in which the IKK-target serine residues of p105 were substituted with alanine. Nfkb1(SSAA/SSAA) mice had far fewer CD4(+) regulatory and memory T cells because of cell-autonomous defects. These T cell subtypes require activation of NF-kappa B by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappa B in CD4(+) T cells and proliferation of CD4(+) T cells after stimulation of the T cell antigen receptor. The Nfkb1(SSAA) mutation also blocked the ability of CD4(+) T cells to provide help to wild-type B cells during a primary antibody response. IKK-induced p105 proteolysis is therefore essential for optimal T cell antigen receptor-induced activation of NF-kappa B and mature CD4(+) T cell function.

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