Page last updated: 2024-10-24

negative regulation of positive thymic T cell selection

Definition

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.'
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Proteins (1)

ProteinDefinitionTaxonomy
Tyrosine-protein phosphatase non-receptor type 2A tyrosine-protein phosphatase non-receptor type 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17706]Homo sapiens (human)

Compounds (30)

CompoundDefinitionClassesRoles
5-iodo-2-(oxaloamino)benzoic acidorganoiodine compound
lithocholic acidlithocholate : 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 acidcyclic terpene ketone;
hydroxy monocarboxylic acid;
pentacyclic triterpenoid
immunomodulator;
plant metabolite
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
vanadatesvanadate(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 acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
geroprotector;
plant metabolite
madecassic acidmonocarboxylic acid;
pentacyclic triterpenoid;
tetrol
antioxidant;
plant metabolite
maslinic acid(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoriadihydroxy monocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
plant metabolite
geniposideterpene glycoside
asiatic acidmonocarboxylic acid;
pentacyclic triterpenoid;
triol
angiogenesis modulating agent;
metabolite
celastrolmonocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
boswellic acidboswellic acid: ursane type; RN given refers to (3alpha,4beta)-isomer; active principle of salai guggal; see also record for salai guggaltriterpenoid
procurcumenolprocurcumenol: 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 sourcesesquiterpenoid
pinocembrin
genipiniridoid monoterpenoidanti-inflammatory agent;
antioxidant;
apoptosis inhibitor;
cross-linking reagent;
hepatotoxic agent;
uncoupling protein inhibitor
2-(oxaloamino)benzoic acid(oxaloamino)benzoic acid
chlorogenic acidcaffeoylquinic 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
tocopherylquinonetocopherylquinone: RN refers to (3R-(3R*,7R*,11R*))-isomer; structure
illudalic acidilludalic acid: isolated from Clitocybe illudens; structure in first source
eupatoriopicrinegermacranolide
2-amino-6-chloropurine6-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 acidtriterpenoidmetabolite
11-keto-boswellic acid
3-epioleanolic acidtriterpenoidmetabolite
oleanonic acidoleanonic acid: structure in first source
zedoarondiolzedoarondiol: structure in first source
formylchromoneformylchromone: structure in first source
rk 682
variabilinvariabilin: an RGD-containing antagonist of glycoprotein IIb-IIIa from the hard tick, Dermacentor variabilis; amino acid sequence given in first source