Impaired immunoproteasome assembly and immune responses in PA28-/- mice.
In vitro PA28 binds and activates proteasomes. It is shown here that mice with a disrupted PA28b gene lack PA28a and PA28b polypeptides, demonstrating that PA28 functions as a hetero-oligomer in vivo. Processing of antigenic epitopes derived from exogenous or endogenous antigens is altered in PA28-/- mice. Cytotoxic T lymphocyte responses are impaired, and assembly of immunoproteasomes is greatly inhibited in mice lacking PA28. These results show that PA28 is necessary for immunoproteasome assembly and is required for efficient antigen processing, thus demonstrating the importance of PA28-mediated proteasome function in immune responses.
Preckel
T
T
The R. W. Johnson Pharmaceutical Research Institute, 3210 Merryfield Row, San Diego, CA 92121, USA.
Fung-Leung
W P
WP
Cai
Z
Z
Vitiello
A
A
Salter-Cid
L
L
Winqvist
O
O
Wolfe
T G
TG
Von Herrath
M
M
Angulo
A
A
Ghazal
P
P
Lee
J D
JD
Fourie
A M
AM
Wu
Y
Y
Pang
J
J
Ngo
K
K
Peterson
P A
PA
Früh
K
K
Yang
Y
Y
D000818:Animals; D017951:Antigen Presentation; D001324:Autoantigens; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D020536:Enzyme Activators / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006182:H-Y Antigen / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000494:pharmacology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D018146:Muromegalovirus / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D001324:Autoantigens; D020536:Enzyme Activators; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D015395:Histocompatibility Antigens Class I; C099558:Ki antigen; D009097:Multienzyme Complexes; D010446:Peptide Fragments; D011506:Proteins; D010047:Ovalbumin; D007372:Interferons; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C486213:Psme1 protein, mouse