title: Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice.
abstract: Loading of peptides onto major histocompatibility complex class I molecules involves a multifactorial complex that includes tapasin (TPN), a membrane protein that tethers empty class I glycoproteins to the transporter associated with antigen processing. To evaluate the in vivo role of TPN, we have generated Tpn mutant mice. In these animals, most class I molecules exit the endoplasmic reticulum (ER) in the absence of stably bound peptides. Consequently, mutant animals have defects in class I cell surface expression, antigen presentation, CD8+ T cell development, and immune responses. These findings reveal a critical role of TPN for ER retention of empty class I molecules. Tpn mutant animals should prove useful for studies on alternative antigen-processing pathways that involve post-ER peptide loading.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. grandea@mcmail.vanderbilt.edu
authors.forename: A G
authors.initials: AG
authors.lastname: Grandea
authors.forename: T N
authors.initials: TN
authors.lastname: Golovina
authors.forename: S E
authors.initials: SE
authors.lastname: Hamilton
authors.forename: V
authors.initials: V
authors.lastname: Sriram
authors.forename: T
authors.initials: T
authors.lastname: Spies
authors.forename: R R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: J T
authors.initials: JT
authors.lastname: Harty
authors.forename: L C
authors.initials: LC
authors.lastname: Eisenlohr
authors.forename: L
authors.initials: L
authors.lastname: Van Kaer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D017920:Antiporters / Q000235:genetics* / Q000276:immunology; D001692:Biological Transport / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology; D026901:Membrane Transport Proteins; D051379:Mice; D009154:Mutation
chemical_list: D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C107762:tapasin