Immune defects in 28-kDa proteasome activator gamma-deficient mice.
Protein complexes of the 28-kDa proteasome activator (PA28) family activate the proteasome and may alter proteasome cleavage specificity. Initial investigations have demonstrated a role for the IFN-gamma-inducible PA28alpha/beta complex in Ag processing. Although the noninducible and predominantly nuclear PA28gamma complex has been implicated in affecting proteasome-dependent signaling pathways, such as control of the mitotic cell cycle, there is no previous evidence demonstrating a role for this structure in Ag processing. We therefore generated PA28gamma-deficient mice and investigated their immune function. PA28gamma(-/-) mice display a slight reduction in CD8+ T cell numbers and do not effectively clear a pulmonary fungal infection. However, T cell responses in two viral infection models appear normal in both magnitude and the hierarchy of antigenic epitopes recognized. We conclude that PA28gamma(-/-) mice, like PA28alpha(-/-)/beta(-/-) mice, are deficient in the processing of only specific Ags.
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OH 45267, USA.
Lance F
LF
Barton
Herbert A
HA
Runnels
Todd D
TD
Schell
Yunjung
Y
Cho
Reta
R
Gibbons
Satvir S
SS
Tevethia
George S
GS
Deepe
John J
JJ
Monaco
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000957:Antigens, Viral, Tumor / Q000276:immunology; D001324:Autoantigens; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D018390:Gene Targeting; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006658:Histoplasma / Q000276:immunology; D006660:Histoplasmosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D013539:Simian virus 40 / Q000276:immunology; D015430:Weight Gain / Q000235:genetics
D000957:Antigens, Viral, Tumor; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C099558:Ki antigen; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex