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Nat Immunol. 2009 Jan;10(1):38-47. doi: 10.1038/ni.1685. Epub 2008 Dec 7.

Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation.

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Division of Immune Cell Biology, National Institute for Medical Research, London NW7 1AA, UK.


To investigate the importance of proteolysis of NF-kappaB1 p105 induced by the kinase IKK in activation of the transcription factor NF-kappaB, 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-kappaB by the T cell antigen receptor for their generation, and the Nfkb1(SSAA) mutation resulted in less activation of NF-kappaB 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-kappaB and mature CD4+ T cell function.

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