Peptide loading complex

A PLC assembly consists of seven subunits, including the transporters associated with antigen processing (TAP1 and TAP2 – jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin.

After final quality control, during which MHC-I heterodimers undergo peptide editing, stable peptide–MHC-I complexes are released to the cell surface for T-cell recognition.

The PLC can serve a large variety of MHC-I allomorphs, thus playing a central role in the differentiation and priming of T lymphocytes, and in controlling viral infections and tumour development.

Both intramolecular domains are coupled to each other and when ATP binding is in progress, conformational changes in the TMDs allow proteasomal degradation products to move across the membrane.

[4] Cresswell and co-workers first discovered tapasin (TAP-associated glycoprotein) as a 48 kDa protein in complexes isolated with TAP1 antibodies from digitonin lysates of human B lymphoblastoid cells.

Studies of a tapasin-deficient cell line and from mice bearing a disrupted tapasin gene, the short-lived complex of class I molecules.

[clarification needed] Tapasin and TAP are very important for the stabilization of the class I molecules and also for the optimization of the peptide presented to cytotoxic T cells.

[7] A PLC-independent tapasin homologue protein named TAPBPR[4] was found that has the ability to act as a second MHC-I specific peptide proofreader or editor, but does not possess a transmembrane domain.

This translocation of TAP facilitates its opening out into an ER luminal cavity, edged by standard membrane entry points such as those for tapasin and MHC-I.