Molecular architecture of the MHC I peptide-loading complex: one tapasin molecule is essential and sufficient for antigen processing

The loading of antigen-derived peptides onto MHC class I molecules for presentation to cytotoxic T cells is a key process in adaptive immune defense. Loading of MHC I is achieved by a sophisticated machin- ery, the peptide-loading complex (PLC), which is orga- nized around the transporter associated with antigen processing (TAP) with the help of several auxiliary pro- teins. As an essential adapter protein recruiting MHC I molecules to TAP, tapasin catalyzes peptide loading of MHC I. However, the exact stoichiometry and basic molecular architecture of TAP and tapasin within the PLC remains elusive. Here, we demonstrate that two tapasin molecules are assembled in the PLC, with one tapasin bound to each TAP subunit. However, one tapasin mole- cule bound either to TAP1 or TAP2 is sufficient for efficient MHC I antigen presentation. By specifically blocking the interaction between tapasin-MHC I com- plexes and the translocation complex TAP, the MHC I surface expression is impaired to the same extent as with soluble tapasin. Thus, the proximity of the peptide sup- plier TAP to the acceptor MHC I is crucial for antigen processing. In summary, the human PLC consists maxi- mally of 2tapasin-ERp57/MHC I per TAP complex, but one tapasin-ERp57/MHC I in the PLC is essential and sufficient for antigen processing.—Hulpke, S., Baldauf, C., Tampe, R. Molecular architecture of the MHC I peptide-loading complex: one tapasin molecule is essen- tial and sufficient for antigen processing. FASEB J. 26, 000-000 (2012). www.fasebj.org