Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

Even Walseng, Kazuyuki Furuta, Berta Bosch, Karis A. Weih, Yohei Matsuki, Oddmund Bakke, Satoshi Ishido, Paul A. Roche

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March- I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I- deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II- specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitindependent degradation of internalized pMHC-II.

Original languageEnglish
Pages (from-to)20465-20470
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number47
DOIs
Publication statusPublished - Nov 23 2010
Externally publishedYes

Fingerprint

Ubiquitination
Dendritic Cells
Peptides
Ubiquitin-Protein Ligases
Endocytosis
Half-Life
Cell Survival
Cell Membrane
T-Lymphocytes
Membranes

ASJC Scopus subject areas

  • General

Cite this

Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. / Walseng, Even; Furuta, Kazuyuki; Bosch, Berta; Weih, Karis A.; Matsuki, Yohei; Bakke, Oddmund; Ishido, Satoshi; Roche, Paul A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 47, 23.11.2010, p. 20465-20470.

Research output: Contribution to journalArticle

Walseng, Even ; Furuta, Kazuyuki ; Bosch, Berta ; Weih, Karis A. ; Matsuki, Yohei ; Bakke, Oddmund ; Ishido, Satoshi ; Roche, Paul A. / Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 47. pp. 20465-20470.
@article{6dc67899acbb4c7ebc8b0d4f347971e2,
title = "Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells",
abstract = "The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March- I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I- deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II- specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitindependent degradation of internalized pMHC-II.",
author = "Even Walseng and Kazuyuki Furuta and Berta Bosch and Weih, {Karis A.} and Yohei Matsuki and Oddmund Bakke and Satoshi Ishido and Roche, {Paul A.}",
year = "2010",
month = "11",
day = "23",
doi = "10.1073/pnas.1010990107",
language = "English",
volume = "107",
pages = "20465--20470",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "47",

}

TY - JOUR

T1 - Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells

AU - Walseng, Even

AU - Furuta, Kazuyuki

AU - Bosch, Berta

AU - Weih, Karis A.

AU - Matsuki, Yohei

AU - Bakke, Oddmund

AU - Ishido, Satoshi

AU - Roche, Paul A.

PY - 2010/11/23

Y1 - 2010/11/23

N2 - The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March- I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I- deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II- specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitindependent degradation of internalized pMHC-II.

AB - The expression and turnover of MHC class II-peptide complexes (pMHC-II) on the surface of dendritic cells (DCs) is essential for their ability to activate CD4 T cells efficiently. The half-life of surface pMHC-II is significantly greater in activated (mature) DCs than in resting (immature) DCs, but the molecular mechanism leading to this difference remains unknown. We now show that ubiquitination of pMHC-II by the E3 ubiquitin ligase membrane-associated RING-CH 1 (March-I) regulates surface expression, intracellular distribution, and survival of pMHC-II in DCs. DCs isolated from March- I-KO mice express very high levels of pMHC-II on the plasma membrane even before DC activation. Although ubiquitination does not affect the kinetics of pMHC-II endocytosis from the surface of DCs, the survival of pMHC-II is enhanced in DCs obtained from March-I- deficient and MHC-II ubiquitination-mutant mice. Using pMHC-II- specific mAb, we show that immature DCs generate large amounts of pMHC-II that are remarkably stable under conditions in which pMHC-II ubiquitination is blocked. Thus, the cellular distribution and stability of surface pMHC-II in DCs is regulated by ubiquitindependent degradation of internalized pMHC-II.

UR - http://www.scopus.com/inward/record.url?scp=78650555387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650555387&partnerID=8YFLogxK

U2 - 10.1073/pnas.1010990107

DO - 10.1073/pnas.1010990107

M3 - Article

VL - 107

SP - 20465

EP - 20470

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 47

ER -