Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice.
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.
Grandea
A G
AG
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. grandea@mcmail.vanderbilt.edu
Golovina
T N
TN
Hamilton
S E
SE
Sriram
V
V
Spies
T
T
Brutkiewicz
R R
RR
Harty
J T
JT
Eisenlohr
L C
LC
Van Kaer
L
L
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
D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C107762:tapasin