Preferred Label : 4-1BB-Dependent Immune Response Pathway;
NCIt synonyms : 4-1BB-Dependent Immune Response Pathway;
NCIt related terms : The 4-1BB-dependent immune response;
Alternative definition : BIOCARTA: The activation of T cells requires a co-stimulatory signal with T cell receptor
activation, provided in many cases by activation of CD28 in resting T cells. 4-1BB
(CD137) is a member of the TNF receptor gene family that provides another T cell co-stimulatory
signal. 4-1BB is expressed by activated cytotoxic and helper T cells and its expression
is induced by a variety of T cell stimuli, including activation of the T cell receptor
or stimulation with mitogens. The ligand for 4-1BB (4-1BBL) is induced on activated
antigen-presenting cells including macrophages, activating T cells expressing 4-1BB.
Mice lacking 4-1BB survive and have an altered though functional immune response.
T cells of mice lacking 4-1BB proliferate more rapidly than normal T cells, but have
reduced cytokine secretion. The costimulatory signal provided by 4-1BB may act in
combination with CD28 activation to prolong the T cell response, and may also act
independently of CD28. Stimulation of T cells with the 4-1BB ligand may provide a
therapeutic immune response in the treatment of cancer or viral infection. 4-1BB in
T cells activates several signaling pathways. Like other members of the TNF receptor
family, the 4-1BB receptor does not have an intrinsic kinase activity. TRAF2 is a
signaling adapter that mediates signaling by other members of the TNF receptor family
and that also binds to the cytoplasmic domain of ligand activated 4-1BB to activate
intracellular kinase cascades. TRAF1 also binds to the cytoplasmic domain of 4-1BB
although with lower affinity than TRAF2. One downstream effector activated by 4-1BB
through TRAF2 is the transcription factor NF-kB. 4-1BB also activates map kinase pathways,
including p38 and JNK activation. ASK1 dependent pathways can activate both p38 and
JNK, and dominant negative ASK1 blocks their activation. Other kinase pathways may
also be involved in 4-1BB activation of p38 and JNK, such as activation of germinal
center kinase (GCK) or related kinases involved in activation of JNK and p38 by TNF.
Map kinase activation along with NF-kB activation results in transcriptional activation
of cytokine genes involved in T cell activation and signaling. The co-stimulatory
signaling provided by 4-1BB shares some features with CD28 signaling, providing an
explanation for the ability of 4-1BB to replace the CD28 costimulatory signal in some
settings. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_41bbPathway;
Origin ID : C39277;
UMLS CUI : C1521330;
Semantic type(s)
has_gene_product_element
pathway_has_gene_element