S. Murata et al., Immunoproteasome assembly and antigen presentation in mice lacking both PA28 alpha and PA28 beta, EMBO J, 20(21), 2001, pp. 5898-5907
Two members of the proteasome activator, PA28 alpha and PA28 beta, form a h
eteropolymer that binds to both ends of the 20S proteasome. Evidence in vit
ro indicates that this interferon-gamma (IFN-gamma)-inducible heteropolymer
is involved in the processing of intracellular antigens, but its functions
in vivo remain elusive. To investigate the role of PA28 alpha/beta in vivo
, we generated mice deficient in both PA28 alpha and PA28 beta genes. The A
TP-dependent proteolytic activities were decreased in PA28 alpha (-/-)/beta
(-/-) cells, suggesting that 'hybrid proteasomes' are involved in protein
degradation. Treatment of PA28 alpha (-/-)/beta (-/-) cells with IFN-gamma
resulted in sufficient induction of the 'immunoproteasome'. Moreover, splen
ocytes from PA28 alpha (-/-)/beta (-/-) mice displayed no apparent defects
in processing of ovalbumin. These results are in marked contrast to the pre
vious finding that immunoproteasome assembly and immune responses were impa
ired in PA28 beta (-/-) mice. PA28 alpha (-/-)/beta (-/-) mice also showed
apparently normal immune responses against infection with influenza A virus
. However, they almost completely lost the ability to process a melanoma an
tigen TRP2-derived peptide. Hence, PA28 alpha/beta is not a prerequisite fo
r antigen presentation in general, but plays an essential role for the proc
essing of certain antigens.