Immune defects in 28-kDa proteasome activator gamma-deficient mice. Journal   Journal of immunology (Baltimore, Md. : 1950) Citation   J Immunol. 172(6):3948-54 Publication date   2004 Mar 15 Authors   Barton LF Runnels HA Schell TD Cho Y Gibbons R Tevethia SS Deepe GS Monaco JJ Investigators   Todd Schell Satvir S. Tevethia Grant agencies   National Institute of Allergy and Infectious Diseases National Cancer Institute Grants   NIAID AI34361 NIAID AI42747 NCI CA25000 MeSH headings   Antigen Presentation Cysteine Endopeptidases Immunologic Deficiency Syndromes Multienzyme Complexes Nuclear Proteins MeSH qualifiers   genetics metabolism deficiency Abstract   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.