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

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 pathway not requiring TAP (transporter associated with antigen processing). The peptide is typically a fragment of a larger exogenous protein which has been degraded within the cell. 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-independent, is a specialized pathway that allows cells to display foreign peptides on their surface, even in the absence of the transporter associated with antigen processing (TAP). This pathway bypasses the classical MHC class I antigen presentation route that relies on TAP to transport peptides from the cytoplasm to the endoplasmic reticulum (ER). Instead, it utilizes alternative mechanisms to deliver exogenous peptides directly into the ER, where they can bind to MHC class I molecules. Here's a detailed breakdown of this process:

1. **Internalization of Exogenous Antigen:** The process begins with the uptake of exogenous antigen by cells through endocytosis. This can occur through various mechanisms, including phagocytosis (for larger particles) or pinocytosis (for smaller particles). The internalized antigen is then enclosed within endosomes.

2. **Endosomal Processing:** Inside the endosomes, the antigen undergoes degradation by proteases, enzymes that break down proteins into smaller peptides. These proteases are typically acidic hydrolases, as the pH within the endosomes is acidic.

3. **Transport to the ER:** The generated peptides are then transported from the endosomes to the ER. This transport step is where the TAP-independent pathway diverges from the classical route. Instead of relying on TAP, this pathway utilizes alternative mechanisms like:
- **Direct Transport:** Some peptides might be able to directly traverse the endosomal membrane and enter the ER.
- **ER-associated degradation (ERAD):** This pathway involves the retrograde transport of peptides from the endoplasmic reticulum to the cytosol, where they can be degraded by proteasomes. The generated peptides can then be retrotranslocated back to the ER, bypassing the need for TAP.
- **Other Non-classical Transporters:** There might be other, as yet unidentified, transporters that directly shuttle peptides from endosomes to the ER.

4. **MHC Class I Loading:** Once in the ER, the peptides encounter MHC class I molecules. These molecules are composed of a heavy chain and a light chain (beta-2 microglobulin) and have a groove where peptides can bind. The peptides generated through the TAP-independent pathway can bind to the MHC class I molecules within the ER.

5. **Chaperone Assistance:** Various chaperones, including tapasin, calreticulin, and ERp57, assist in the proper loading and folding of MHC class I-peptide complexes within the ER.

6. **Golgi Translocation and Surface Expression:** The MHC class I-peptide complexes are then transported through the Golgi apparatus, where they undergo further modifications and are eventually delivered to the cell surface.

7. **Antigen Presentation:** The MHC class I-peptide complexes displayed on the cell surface can now be recognized by CD8+ T cells, which are a type of immune cell responsible for killing infected or cancerous cells. The interaction between the MHC class I-peptide complex and the CD8+ T cell receptor triggers an immune response, leading to the elimination of the target cell.

**Significance of the TAP-independent pathway:**

- **Expansion of the antigen repertoire:** By bypassing the need for TAP, this pathway allows cells to present a wider range of peptides to CD8+ T cells, including peptides that are not normally processed by the classical MHC class I pathway.
- **Immune evasion:** Some pathogens have evolved mechanisms to evade the classical TAP-dependent pathway, such as inhibiting TAP function. However, the TAP-independent pathway can provide a backup route for presenting antigens derived from these pathogens, enabling the immune system to recognize and eliminate them.
- **Tumor surveillance:** This pathway is crucial for the presentation of tumor-associated antigens, which can trigger an immune response against cancerous cells.

**Overall, the TAP-independent pathway is an important and intricate mechanism that allows cells to present exogenous antigens via MHC class I in a TAP-independent manner. This pathway contributes to the immune system's ability to recognize and eliminate pathogens, as well as to control tumor growth.**'
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