antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent

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 following intracellular transport via a TAP (transporter associated with antigen processing) pathway. The peptide is typically a fragment of a larger exogenous protein which has been degraded within the cell and is dependent on TAP transport from the cytosol to ER for association with the MHC class I molecule. Class I here refers to classical class I molecules. [GOC:add, PMID:15224093, PMID:15771591, PMID:16181335]

Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent, is a complex process that involves the following steps:

1. **Antigen uptake:** Exogenous antigens, such as viral proteins or bacterial toxins, are taken up by antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. This uptake can occur through various mechanisms, including phagocytosis, endocytosis, and macropinocytosis.

2. **Antigen degradation:** Once inside the APC, exogenous antigens are degraded into small peptides by proteasomes, large protein complexes that break down proteins into smaller fragments. The proteasome is a barrel-shaped structure that contains proteolytic enzymes that cleave peptide bonds.

3. **Peptide transport:** The generated peptides are then transported from the cytosol into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), a heterodimeric ATP-binding cassette (ABC) transporter. TAP is a highly selective transporter that preferentially binds peptides of 8-11 amino acids in length, the optimal size for MHC class I binding.

4. **MHC class I loading:** In the ER, peptides bind to MHC class I molecules, which are heterodimers composed of a heavy chain and a light chain called beta-2-microglobulin. Peptide loading onto MHC class I molecules is a complex process that is facilitated by chaperone proteins, such as calreticulin, tapasin, and ERp57. These chaperones ensure that the peptide binding groove of MHC class I is properly folded and that the appropriate peptides are loaded.

5. **MHC class I transport and surface expression:** Once the peptide-MHC class I complex is assembled, it is transported from the ER to the Golgi apparatus and then to the cell surface. This transport is mediated by the secretory pathway.

6. **T cell activation:** The peptide-MHC class I complex on the surface of the APC can interact with the T cell receptor (TCR) on CD8+ cytotoxic T lymphocytes (CTLs). This interaction triggers a cascade of signaling events within the CTL, leading to its activation and the subsequent killing of infected or cancerous cells.

In summary, TAP-dependent antigen processing and presentation via MHC class I is an essential pathway for immune surveillance. It allows the immune system to recognize and eliminate cells infected with intracellular pathogens or harboring tumor-associated antigens. This process involves the degradation of exogenous antigens, the transport of peptides into the ER, the loading of peptides onto MHC class I molecules, and the presentation of these peptide-MHC class I complexes on the cell surface for recognition by CTLs.'
"

Proteins (2)

Compounds (108)