Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of positive thymic T cell selection. [GOC:TermGenie, PMID:22080863]
Negative regulation of positive thymic T cell selection is a critical process that ensures the proper development and maturation of T cells in the thymus. It involves the downregulation of signals that promote the survival and differentiation of T cells that recognize self-antigens with too high affinity. This ensures that the immune system does not target and destroy its own tissues. The process involves several key steps:
1. **Thymic T cell selection:** During their development in the thymus, T cells undergo a process called selection, where they are tested for their ability to recognize and bind to self-antigens presented by thymic epithelial cells. T cells that recognize self-antigens with too high affinity are eliminated through a process called negative selection, while those that recognize self-antigens with low affinity survive and mature.
2. **Signal transduction pathways:** The recognition of self-antigens by T cell receptors (TCRs) triggers downstream signaling pathways that lead to the activation of transcription factors and the expression of genes involved in T cell survival, proliferation, and differentiation. In the case of negative selection, these pathways are often downregulated or inhibited.
3. **Inhibitory receptors:** Several inhibitory receptors, such as CTLA-4 and PD-1, are expressed on T cells and can bind to ligands on antigen-presenting cells. These interactions trigger signaling pathways that inhibit TCR-mediated activation and promote T cell anergy or apoptosis.
4. **Apoptosis:** If the signals that promote T cell survival are sufficiently downregulated, the T cell undergoes programmed cell death, or apoptosis.
5. **T cell anergy:** In some cases, T cells may not undergo apoptosis but instead become anergic, meaning they are unable to respond to subsequent stimulation by their cognate antigen.
6. **Regulatory T cells:** Another important mechanism of negative regulation is the development of regulatory T cells (Tregs). These cells express the transcription factor Foxp3 and are specialized to suppress the activity of other T cells, including those that may have escaped negative selection.
Overall, negative regulation of positive thymic T cell selection is a complex and tightly regulated process that ensures the development of a self-tolerant T cell repertoire. It involves a variety of mechanisms, including inhibitory receptors, signal transduction pathways, and the development of Tregs, that act to eliminate or suppress T cells that recognize self-antigens with too high affinity. This process is essential for maintaining immune homeostasis and preventing autoimmune disease.'
"
Protein | Definition | Taxonomy |
---|---|---|
Tyrosine-protein phosphatase non-receptor type 2 | A tyrosine-protein phosphatase non-receptor type 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17706] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
5-iodo-2-(oxaloamino)benzoic acid | organoiodine compound | ||
lithocholic acid | lithocholate : A bile acid anion that is the conjugate base of lithocholic acid. lithocholic acid : A monohydroxy-5beta-cholanic acid with a alpha-hydroxy substituent at position 3. It is a bile acid obtained from chenodeoxycholic acid by bacterial action. Lithocholic Acid: A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic. | bile acid; C24-steroid; monohydroxy-5beta-cholanic acid | geroprotector; human metabolite; mouse metabolite |
glycyrrhetinic acid | cyclic terpene ketone; hydroxy monocarboxylic acid; pentacyclic triterpenoid | immunomodulator; plant metabolite | |
oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
vanadates | vanadate(3-) : A vanadium oxoanion that is a trianion with formula VO4 in which the vanadium is in the +5 oxidation state and is attached to four oxygen atoms. Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects. | trivalent inorganic anion; vanadium oxoanion | EC 3.1.3.1 (alkaline phosphatase) inhibitor; EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor; EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor; EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor |
ursolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | geroprotector; plant metabolite | |
madecassic acid | monocarboxylic acid; pentacyclic triterpenoid; tetrol | antioxidant; plant metabolite | |
maslinic acid | (2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoria | dihydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory agent; antineoplastic agent; antioxidant; plant metabolite |
geniposide | terpene glycoside | ||
asiatic acid | monocarboxylic acid; pentacyclic triterpenoid; triol | angiogenesis modulating agent; metabolite | |
celastrol | monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory drug; antineoplastic agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Hsp90 inhibitor; metabolite | |
cryptotanshinone | cryptotanshinone: from Salvia miltiorrhiza | abietane diterpenoid | anticoronaviral agent |
boswellic acid | boswellic acid: ursane type; RN given refers to (3alpha,4beta)-isomer; active principle of salai guggal; see also record for salai guggal | triterpenoid | |
procurcumenol | procurcumenol: RN given for (1S-(1alpha,3abeta,8aalpha))-isomer; epiprocurcumenol is the (1S-(1alpha,3aalpha,8aalpha))-isomer; a TNF-alpha antagonist isolated from Curcuma zedoaria; structure in first source | sesquiterpenoid | |
pinocembrin | |||
genipin | iridoid monoterpenoid | anti-inflammatory agent; antioxidant; apoptosis inhibitor; cross-linking reagent; hepatotoxic agent; uncoupling protein inhibitor | |
2-(oxaloamino)benzoic acid | (oxaloamino)benzoic acid | ||
chlorogenic acid | caffeoylquinic acid: Antiviral Agent; structure in first source chlorogenate : A monocarboxylic acid anion that is the conjugate base of chlorogenic acid; major species at pH 7.3. | cinnamate ester; tannin | food component; plant metabolite |
tocopherylquinone | tocopherylquinone: RN refers to (3R-(3R*,7R*,11R*))-isomer; structure | ||
illudalic acid | illudalic acid: isolated from Clitocybe illudens; structure in first source | ||
eupatoriopicrine | germacranolide | ||
2-amino-6-chloropurine | 6-chloroguanine : An organochlorine compound that is 7H-purin-2-amine substituted by a chloro group at position 6. 6-chloroguanine: an antimalarial that inhibits hypoxanthine-guanine-xanthine phosphoribosyltransferase; structure in first source | 2-aminopurines; organochlorine compound | |
corosolic acid | triterpenoid | metabolite | |
11-keto-boswellic acid | |||
3-epioleanolic acid | triterpenoid | metabolite | |
oleanonic acid | oleanonic acid: structure in first source | ||
zedoarondiol | zedoarondiol: structure in first source | ||
formylchromone | formylchromone: structure in first source | ||
rk 682 | |||
variabilin | variabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source |