antigen processing and presentation of endogenous peptide antigen via MHC class I

Definition

Target type: biologicalprocess

The process in which an antigen-presenting cell expresses a peptide antigen of endogenous 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]

Endogenous antigen processing and presentation via MHC class I is a complex process that allows cells to display fragments of intracellular proteins, known as peptides, on their surface for recognition by cytotoxic T lymphocytes (CTLs). This process is essential for the immune system to detect and eliminate cells infected with viruses, bacteria, or other pathogens, as well as tumor cells.

The process begins with the degradation of intracellular proteins within the cytoplasm. This degradation can occur through various pathways, including the proteasome, a large protein complex that breaks down proteins into short peptides. The proteasome is highly regulated and can be influenced by factors like interferon-gamma (IFN-γ), a cytokine that enhances its activity.

The generated peptides are then transported into the endoplasmic reticulum (ER), a network of membranes within the cell. This transport is mediated by the transporter associated with antigen processing (TAP) complex, a heterodimer that recognizes and translocates peptides across the ER membrane. The TAP complex exhibits a preference for peptides with a specific length and amino acid sequence, ensuring that only relevant peptides are transported.

Within the ER, peptides encounter major histocompatibility complex (MHC) class I molecules. MHC class I molecules are cell surface receptors that present peptides to CTLs. They are composed of a heavy chain and a light chain called β2-microglobulin. The heavy chain consists of three domains: α1, α2, and α3. The α1 and α2 domains form a peptide-binding groove where peptides are loaded.

The peptide loading process is facilitated by chaperone proteins, such as tapasin, calreticulin, and ERp57. These proteins help to stabilize the MHC class I molecule and ensure proper peptide binding. The peptide must be the right size and sequence to fit into the groove and form a stable complex.

Once loaded with a peptide, the MHC class I molecule is transported to the cell surface via the Golgi apparatus. At the cell surface, the MHC class I-peptide complex is displayed for recognition by CTLs.

CTLs express T cell receptors (TCRs) that recognize specific MHC class I-peptide complexes. When a TCR encounters its cognate antigen, it triggers a signaling cascade that leads to the activation of the CTL. Activated CTLs can then kill the target cell through the release of cytotoxic granules containing perforin and granzyme.

In summary, the process of endogenous antigen processing and presentation via MHC class I involves the degradation of intracellular proteins, peptide transport into the ER, peptide loading onto MHC class I molecules, and display of the MHC class I-peptide complex on the cell surface for recognition by CTLs. This process is essential for the immune system to detect and eliminate cells infected with pathogens or harboring abnormal proteins.'
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Proteins (4)

Compounds (17)