Science · 1997 · 522 citations · 30 references
Life SciencesImmunologyMolecular BiologyCellular ImmunologyImmunogeneticsProtein-protein InteractionsAntigen Presentation RegulationHistocompatibility AntigensHuman Leukocyte Antigen SystemMajor Histocompatibility ComplexProtein Complex AssemblyClass I Histocompatibility AntigensMajor Histocompatibility Complex (Mhc) PresentationMajor Histocompatibility Complex Class I Antigen ProcessingMajor Histocompatibility Complex Class I PresentationMhc Class I MoleculesTap Transporter FunctionTapasin FunctionTransmembrane Domains
Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact with the transporter associated with antigen processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be a transmembrane glycoprotein encoded by an MHC-linked gene. It is a member of the immunoglobulin superfamily with a probable cytoplasmic endoplasmic reticulum retention signal. Up to four MHC class I-tapasin complexes were found to bind to each TAP molecule. Expression of tapasin in a negative mutant human cell line (220) restored class I-TAP association and normal class I cell surface expression. Tapasin expression also corrected the defective recognition of virus-infected 220 cells by class I-restricted cytotoxic T cells, establishing a critical functional role for tapasin in MHC class I-restricted antigen processing.
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