Proteolysis of NF-kappaB1 p105 is essential for T cell antigen receptor-induced proliferation.
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.
Sriskantharajah
Srividya
S
Division of Immune Cell Biology, National Institute for Medical Research, London NW7 1AA, UK.
Belich
Monica P
MP
Papoutsopoulou
Stamatia
S
Janzen
Julia
J
Tybulewicz
Victor
V
Seddon
Benedict
B
Ley
Steven C
SC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D051550:I-kappa B Kinase / Q000378:metabolism*; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D052002:NF-kappa B p50 Subunit; D011948:Receptors, Antigen, T-Cell; C073701:Nfkb1 protein, mouse; D051550:I-kappa B Kinase