Mechanistic aspects of tapasin-mediated antigen presentation revealed by structure of a tapasin/MHC-I complex

Abstract T cell immunity to viruses and cancers is crucially dependent on the surface display of major histocompatibility complex class I (MHC-I) molecules selectively loaded with high affinity peptides. Peptide loading occurs in ER within a multimolecular assembly known as peptide (PLC). A critical component PLC tapasin, 45 kDa membrane glycoprotein whose absence expression stability MHC-I are greatly reduced. To determine mechanistic basis tapasin-mediated loading, we determined crystal structures human tapasin HLA-B44:05 well complexed each two well-characterized antibodies. The tapasin-stabilized receptive state characterized by distortions binding groove, destabilization b 2-microglobulin interaction, rearrangements proximal Ig domains, all which reversed binding. Additionally, structural footprints anti-tapasin antibodies confirm previous functional assays together tapasin/MHC-I mutagenesis data reveal dynamic aspects function. Supported Intramural Research Program, NIAID, NIH.