Deciphering MHC I chaperone complexes

• Applicant: Professor Dr. Robert Tampé
• Subject Area: Biochemistry
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407041508

Adaptive immunity can detect and clear pathogens as well as malignantly or virally transformed cells. A malfunction, on the other hand, leads to tumor progression, chronic infections, or autoimmune diseases. Peptides derived from proteasomal degradation and presented by major histocompatibility complex class I (MHC-I) molecules are essential for mounting a specific immune response by cytotoxic Tlymphocytes. The peptide-loading complex (PLC) plays a crucial role in the effective immune surveillance by recognizing, translocating, and chaperoning antigenic peptides onto MHC-I molecules. Forming a gigantic multisubunit membrane complex, the PLC consists of the transporter associated with antigen processing TAP1/2, the three ER chaperones tapasin, ERp57, and calreticulin, as well as the MHC-I heavy chain/b2m heterodimer. The key role of the PLC in adaptive immunity is emphasized by the fact that various viruses have developed extensive ways to interfere with PLC function. This high-risk/high-gain project aims to gain a holistic understanding of the PLC and other MHC-I chaperone complexes. The insights into architecture and dynamic reorganization of the MHC-I chaperone and editing complexes will ultimately pave the way for unraveling general principles of intracellular membrane-embedded transient multiprotein assemblies in the human body.

• DFG Programme: Reinhart Koselleck Projects