The assembly of major histocompatibility complex (MHC) class I molecules with peptides occurs within the ER with the aid of multiple proteins that associate to form a 'peptide loading complex' (PLC). The formation of this PLC is a critical step in efficient generation of peptide-MHC class I complexes for transport to the cell surface. The PLC is comprised of the heterodimeric transporter associated with antigen processing (TAP), MHC class I molecules, tapasin, calreticulin and ERp57. Previous studies examining lateral mobility, as measured by effective diffusion coefficient (Deff), have demonstrated that the PLC diffuses slower than can be accounted for by the known members and estimated stoichiometry of the PLC. These data are consistent with the hypothesis that there may be as yet unidentified proteins or protein complexes that associate with the PLC to account for its low Deff value. Our preliminary data demonstrate that tapasin reduces the lateral mobility of TAP suggesting that tapasin may play a key role in interacting with other proteins. We have identified a novel interacting partner of tapasin. Since tapasin is a chaperone dedicated to promoting MHC class I assembly and export we hypothesize that interactions between tapasin and currently unidentified proteins are important for optimal MHC class I assembly and may explain the unusually low Deff value of the PLC. Since MHC class I assembly and the PLC are targets of viral genes which aim to evade the immune response, our studies are important to understand the fundamentals of MHC class I assembly which will assist our understanding of how viruses evade immune recognition. ? ? ?
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