MHC class I peptide loading complex

Definition

Target type: cellularcomponent

A large, multisubunit complex which consists of the MHC class I-beta 2 microglobulin dimer, the transporter associated with antigen presentation (TAP), tapasin (an MHC-encoded membrane protein), the chaperone calreticulin and the thiol oxidoreductase ERp57. Functions in the assembly of peptides with newly synthesized MHC class I molecules. [GOC:jl, PMID:10631934]

The MHC class I peptide loading complex (PLC) is a multi-protein complex that is essential for the generation of MHC class I-restricted peptides, which are displayed on the surface of cells and recognized by cytotoxic T lymphocytes (CTLs). The PLC assembles in the endoplasmic reticulum (ER) and is composed of the following components:

1. **MHC class I heavy chain:** The heavy chain is the main component of the MHC class I molecule, which is a transmembrane protein composed of three alpha domains (α1, α2, and α3) and a transmembrane region. The α1 and α2 domains form the peptide-binding groove that binds to the antigenic peptide. The α3 domain interacts with the β2-microglobulin (β2m) light chain.
2. **β2-microglobulin (β2m):** β2m is a small protein that associates non-covalently with the α3 domain of the MHC class I heavy chain. It is required for proper folding and stability of the MHC class I molecule.
3. **Tapasin:** Tapasin is a chaperone protein that interacts with both the MHC class I heavy chain and the TAP transporter. It assists in the loading of peptides onto the MHC class I molecule by stabilizing the MHC class I-TAP complex and facilitating peptide transfer.
4. **TAP transporter:** The TAP transporter is a heterodimeric transmembrane protein that translocates peptides from the cytosol into the ER lumen. It is composed of two subunits, TAP1 and TAP2, which form a channel through the ER membrane. The TAP transporter preferentially transports peptides of 8-10 amino acids in length, which are typically derived from degraded proteins.
5. **ERp57:** ERp57 is a thiol oxidoreductase that participates in the folding and assembly of MHC class I molecules. It catalyzes disulfide bond formation in the MHC class I heavy chain, which is required for proper folding and stability.

The PLC facilitates peptide loading onto MHC class I molecules in a stepwise manner:

1. **Peptide transport:** Peptides generated in the cytosol are transported into the ER lumen by the TAP transporter.
2. **MHC class I loading:** The TAP transporter delivers peptides to the MHC class I heavy chain, which is associated with β2m and tapasin.
3. **Peptide selection:** Tapasin facilitates the selection of peptides that bind tightly to the MHC class I molecule.
4. **MHC class I assembly:** Once a peptide has bound to the MHC class I molecule, the complex dissociates from tapasin and is transported to the cell surface.

The PLC plays a critical role in the adaptive immune response by ensuring that the MHC class I molecules present a diverse array of peptides to CTLs. This allows CTLs to recognize and eliminate infected or cancerous cells.'
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Proteins (1)

Compounds (8)