Impaired immunoproteasome assembly and immune responses in PA28-/- mice

T Preckel; W P Fung-Leung; Z Cai; A Vitiello; L Salter-Cid; O Winqvist; T G Wolfe; M Von Herrath; A Angulo; P Ghazal; J D Lee; A M Fourie; Y Wu; J Pang; K Ngo; P A Peterson; K Früh; Y Yang

Impaired immunoproteasome assembly and immune responses in PA28-/- mice

T Preckel, W P Fung-Leung, Z Cai, A Vitiello, L Salter-Cid, O Winqvist, T G Wolfe, M Von Herrath, A Angulo, P Ghazal, J D Lee, A M Fourie, Y Wu, J Pang, K Ngo, P A Peterson, K Früh, Y Yang

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2162-5
Number of pages	4
Journal	Science
Volume	286
Issue number	5447
Publication status	Published - 1999

Keywords / Materials (for Non-textual outputs)

Animals
Antigen Presentation
Autoantigens
Cysteine Endopeptidases
Enzyme Activators
Epitopes, T-Lymphocyte
Female
H-Y Antigen
Herpesviridae Infections
Histocompatibility Antigens Class I
Interferons
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Male
Mice
Multienzyme Complexes
Muromegalovirus
Ovalbumin
Peptide Fragments
Proteasome Endopeptidase Complex
Proteins
T-Lymphocytes, Cytotoxic

Cite this

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title = "Impaired immunoproteasome assembly and immune responses in PA28-/- mice",

abstract = "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.",

keywords = "Animals, Antigen Presentation, Autoantigens, Cysteine Endopeptidases, Enzyme Activators, Epitopes, T-Lymphocyte, Female, H-Y Antigen, Herpesviridae Infections, Histocompatibility Antigens Class I, Interferons, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Male, Mice, Multienzyme Complexes, Muromegalovirus, Ovalbumin, Peptide Fragments, Proteasome Endopeptidase Complex, Proteins, T-Lymphocytes, Cytotoxic",

author = "T Preckel and Fung-Leung, {W P} and Z Cai and A Vitiello and L Salter-Cid and O Winqvist and Wolfe, {T G} and {Von Herrath}, M and A Angulo and P Ghazal and Lee, {J D} and Fourie, {A M} and Y Wu and J Pang and K Ngo and Peterson, {P A} and K Fr{\"u}h and Y Yang",

year = "1999",

language = "English",

volume = "286",

pages = "2162--5",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5447",

}

TY - JOUR

T1 - Impaired immunoproteasome assembly and immune responses in PA28-/- mice

AU - Preckel, T

AU - Fung-Leung, W P

AU - Cai, Z

AU - Vitiello, A

AU - Salter-Cid, L

AU - Winqvist, O

AU - Wolfe, T G

AU - Von Herrath, M

AU - Angulo, A

AU - Ghazal, P

AU - Lee, J D

AU - Fourie, A M

AU - Wu, Y

AU - Pang, J

AU - Ngo, K

AU - Peterson, P A

AU - Früh, K

AU - Yang, Y

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

KW - Animals

KW - Antigen Presentation

KW - Autoantigens

KW - Cysteine Endopeptidases

KW - Enzyme Activators

KW - Epitopes, T-Lymphocyte

KW - Female

KW - H-Y Antigen

KW - Herpesviridae Infections

KW - Histocompatibility Antigens Class I

KW - Interferons

KW - Lymphocytic Choriomeningitis

KW - Lymphocytic choriomeningitis virus

KW - Male

KW - Mice

KW - Multienzyme Complexes

KW - Muromegalovirus

KW - Ovalbumin

KW - Peptide Fragments

KW - Proteasome Endopeptidase Complex

KW - Proteins

KW - T-Lymphocytes, Cytotoxic

M3 - Article

C2 - 10591649

SN - 0036-8075

VL - 286

SP - 2162

EP - 2165

JO - Science

JF - Science

IS - 5447

ER -

Impaired immunoproteasome assembly and immune responses in PA28-/- mice

Abstract

Keywords / Materials (for Non-textual outputs)

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Cite this