antigen processing and presentation of exogenous peptide antigen via MHC class I
Definition
Target type: biologicalprocess
The process in which an antigen-presenting cell expresses a peptide antigen of exogenous origin on its cell surface in association with an MHC class I protein complex. The peptide antigen is typically, but not always, processed from a whole protein. Class I here refers to classical class I molecules. [GOC:add, ISBN:0781735149, PMID:15771591]
The process of antigen processing and presentation of exogenous peptide antigen via MHC class I, also known as cross-presentation, is a crucial mechanism by which the immune system recognizes and responds to pathogens. Here's a detailed explanation:
1. **Antigen Uptake**: Exogenous antigens, such as those from viruses, bacteria, or parasites, enter the cell through various pathways:
* **Endocytosis**: The cell engulfs the antigen through specialized membrane invaginations forming vesicles.
* **Phagocytosis**: Immune cells like macrophages and dendritic cells engulf large particles like bacteria.
* **Macropinocytosis**: Cells take up fluid and dissolved solutes, potentially containing antigens.
2. **Antigen Processing**: Once inside the cell, the antigen undergoes processing to generate peptides suitable for MHC class I presentation:
* **Degradation**: The antigen is broken down into smaller peptides by proteasomes, multi-protein complexes that degrade proteins.
* **TAP Transport**: The peptides generated by the proteasome are transported into the endoplasmic reticulum (ER) via the transporter associated with antigen processing (TAP) complex.
3. **MHC Class I Loading**: In the ER, the peptides interact with MHC class I molecules:
* **Assembly**: MHC class I molecules, composed of α and β2 microglobulin chains, assemble in the ER.
* **Peptide Loading**: The peptide binds to the MHC class I molecule in a groove within the α chain.
* **Chaperones**: Chaperone proteins like calnexin and calreticulin assist in the folding and peptide loading of MHC class I molecules.
4. **MHC Class I Trafficking**: The peptide-loaded MHC class I complex exits the ER and is transported to the cell surface via the Golgi apparatus:
* **Vesicle Transport**: The complex travels within transport vesicles through the Golgi.
* **Quality Control**: The Golgi apparatus ensures proper folding and peptide loading before further transport.
5. **Presentation on the Cell Surface**: The MHC class I complex is displayed on the cell surface, making the peptide accessible to CD8+ T cells:
* **Recognition**: CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), possess T cell receptors (TCRs) that recognize specific peptides presented by MHC class I molecules.
* **Activation**: Upon TCR engagement, the CD8+ T cell becomes activated, leading to the production of effector molecules that eliminate infected or cancerous cells.
This process is critical for the immune system to recognize and eliminate pathogens that reside within cells. The ability to present exogenous antigens via MHC class I allows the immune system to effectively target a wide range of threats.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Macrophage-expressed gene 1 protein | A macrophage-expressed gene 1 protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q2M385] | Homo sapiens (human) |
| High affinity immunoglobulin gamma Fc receptor I | A high affinity immunoglobulin gamma Fc receptor I that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12314] | Homo sapiens (human) |
| HLA class I histocompatibility antigen, A alpha chain | An MHC class I histocompatibility antigen A alpha chain that is encoded in the genome of human. [PRO:DAN] | Homo sapiens (human) |
Compounds (14)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| astemizole | astemizole : A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position. Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects. | benzimidazoles; piperidines | anti-allergic agent; anticoronaviral agent; H1-receptor antagonist |
| embelin | embelin : A member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease. embelin: from Embelia fruit (Myrsinaceae) | dihydroxy-1,4-benzoquinones | antimicrobial agent; antineoplastic agent; hepatitis C protease inhibitor; plant metabolite |
| haloperidol | haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| spiperone | spiperone : An azaspiro compound that is 1,3,8-triazaspiro[4.5]decane which is substituted at positions 1, 4, and 8 by phenyl, oxo, and 4-(p-fluorophenyl)-4-oxobutyl groups, respectively. Spiperone: A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. It has been recommended in the treatment of SCHIZOPHRENIA. | aromatic ketone; azaspiro compound; organofluorine compound; piperidines; tertiary amino compound | alpha-adrenergic antagonist; antipsychotic agent; dopaminergic antagonist; psychotropic drug; serotonergic antagonist |
| raloxifene hydrochloride | raloxifene hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of raloxifene and hydrogen chloride. Raloxifene Hydrochloride: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. | hydrochloride | bone density conservation agent; estrogen antagonist; estrogen receptor modulator |
| trazodone hydrochloride | trazodone hydrochloride : A hydrochloride salt prepared from equimolar amounts of trazodone and hydrogen chloride. Triticum: A plant genus of the family POACEAE that is the source of EDIBLE GRAIN. A hybrid with rye (SECALE CEREALE) is called TRITICALE. The seed is ground into FLOUR and used to make BREAD, and is the source of WHEAT GERM AGGLUTININS. | hydrochloride | adrenergic antagonist; antidepressant; H1-receptor antagonist; sedative; serotonin uptake inhibitor |
| doxazosin mesylate | Cardura: Trade name in United States. | methanesulfonate salt | geroprotector |
| rapanone | rapanone: antiparasitic agent from Rapanea; structure similar to embelin | dihydroxy-1,4-benzoquinones | |
| vatalanib | monochlorobenzenes; phthalazines; pyridines; secondary amino compound | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor; vascular endothelial growth factor receptor antagonist | |
| 5-o-methylembelin | 5-O-methyl embelin : A member of the class of monohydroxy-1,4-benzoquinones that is embelin in which the hydroxy group at position 5 is replaced by a methoxy group. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antileishmanial activity as well as inhibitory activity towards hepatitis C protease. 5-O-methylembelin: extracted from mangrove Aegiceras corniculatum; piscicide; see embelin | enol ether; monohydroxy-1,4-benzoquinones | antileishmanial agent; antineoplastic agent; hepatitis C protease inhibitor; metabolite |
| l 663536 | 3-[3-(tert-butylsulfanyl)-1-(4-chlorobenzyl)-5-(propan-2-yl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid : A member of the class of indoles that is 1H-indole substituted by a isopropyl group at position 5, a tert-butylsulfanediyl group at position 3, a 4-chlorobenzyl group at position 1 and a 2-carboxy-2-methylpropyl group at position 2. It acts as an inhibitor of arachidonate 5-lipoxygenase. MK-886: orally active leukotriene biosynthesis inhibitor | aryl sulfide; indoles; monocarboxylic acid; monochlorobenzenes | antineoplastic agent; EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor; leukotriene antagonist |
| mart-1 antigen | MART-1 Antigen: A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells. | ||
| bms 777607 | N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide: a Met kinase inhibitor; structure in first source | aromatic amide | |
| nms p937 | NMS P937: a polo-like kinase 1 inhibitor; structure in first source |