peptide antigen assembly with MHC class I protein complex

Definition

Target type: biologicalprocess

The binding of a peptide to the antigen binding groove of an MHC class I protein complex. Class I here refers to classical class I molecules. [GOC:add, ISBN:0781735149, PMID:15771591]

The assembly of peptide antigens with MHC class I protein complex is a crucial step in the adaptive immune response, enabling the presentation of intracellular antigens to cytotoxic T lymphocytes (CTLs). This process involves a series of intricate steps that ensure the generation of stable peptide-MHC class I complexes capable of activating CTLs. The process can be summarized in the following steps:

1. **Protein Degradation:** Intracellular proteins are degraded by the proteasome, a multi-subunit protease complex. The proteasome generates short peptides, typically 8-11 amino acids in length, which can potentially bind to MHC class I molecules.

2. **Peptide Transport:** Peptides generated by the proteasome are transported into the endoplasmic reticulum (ER) via the transporter associated with antigen processing (TAP). TAP is a heterodimer composed of TAP1 and TAP2 subunits, which selectively transport peptides with specific characteristics, favoring those with hydrophobic or basic residues at their C-terminus.

3. **MHC Class I Assembly:** MHC class I molecules are assembled in the ER, consisting of a heavy chain, a light chain (beta-2 microglobulin), and a peptide. The heavy chain contains a peptide-binding groove that is initially occupied by a chaperone protein called calnexin. The light chain binds to the heavy chain, and the chaperone protein calreticulin associates with the complex.

4. **Peptide Loading:** TAP delivers peptides into the ER, where they compete for binding to the peptide-binding groove of MHC class I molecules. The chaperones facilitate peptide loading and promote the release of the chaperone proteins. This process is influenced by several factors, including peptide length, amino acid composition, and affinity for the MHC class I molecule.

5. **ER Quality Control:** The ER ensures the stability and proper folding of the MHC class I complex before its transport to the cell surface. The complex undergoes several quality control mechanisms, including the interaction with the chaperone protein tapasin. Tapasin facilitates peptide loading and promotes the dissociation of chaperone proteins.

6. **Transport to the Cell Surface:** After successful assembly and quality control, the peptide-MHC class I complex is transported from the ER to the Golgi apparatus and then to the cell surface. This transport is mediated by the secretory pathway, involving vesicle-mediated trafficking.

7. **Antigen Presentation:** Once expressed on the cell surface, the peptide-MHC class I complex presents the processed antigen to CTLs. CTLs express T cell receptors (TCRs) that recognize specific peptide-MHC class I complexes. Upon recognition, CTLs become activated and can induce target cell lysis, eliminating infected or cancerous cells.'
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Proteins (1)

Compounds (8)