| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory for Infectious Immunity, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan;
Department of Immunology, Toho University School of Medicine, Tokyo, Japan; and
Division of Microbiology, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
We previously reported a novel E3 ubiquitin ligase (E3), designated as c-MIR, which targets B7-2 to lysosomal degradation and down-regulates the B7-2 surface expression through ubiquitination of its cytoplasmic tail. B7-2 is well known as a costimulatory molecule for Ag presentation, suggesting that the manipulation of c-MIR expression modulates immune responses in vivo. To examine this hypothesis, we generated genetically modified mice in which c-MIR was expressed under an invariant chain (Ii) promoter. Dendritic cells derived from genetically engineered mice showed low ability to present Ags. In addition, these mice showed resistance to the onset of experimental autoimmune encephalomyelitis and an impaired development of CD4 T cells in the thymus and the periphery. These findings led us to conclude that MHC class II (MHC II) is an additional target for c-MIR. Indeed, forced expression of c-MIR in several B cell lines down-regulated the surface expression of MHC II, and down-regulation was found to depend on the presence of a single lysine residue in the cytoplasmic tail of the I-A 
-chain. In a reconstitution system using 293T cells, we found that the lysine residue at position 225 in the I-A -chain was ubiquitinated by c-MIR. To our knowledge, c-MIR is the first example of an E3 that is capable of inhibiting MHC II expression. Our findings suggest that c-MIR might potently regulate immune responses in vivo.
This article has been cited by other articles:
|
|
 |
|
  A. De Gassart, V. Camosseto, J. Thibodeau, M. Ceppi, N. Catalan, P. Pierre, and E. Gatti MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation PNAS, March 4, 2008; 105(9): 3491 - 3496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.G. S. Kumar, H. Barriere, C. J. Carbone, J. Liu, G. Swaminathan, P. Xu, Y. Li, D. P. Baker, J. Peng, G. L. Lukacs, et al. Site-specific ubiquitination exposes a linear motif to promote interferon-{alpha} receptor endocytosis J. Cell Biol., December 3, 2007; 179(5): 935 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Young, N. S. Wilson, P. Schnorrer, A. Mount, R. J. Lundie, N. L. La Gruta, B. S. Crabb, G. T. Belz, W. R. Heath, and J. A. Villadangos Dendritic cell preactivation impairs MHC class II presentation of vaccines and endogenous viral antigens PNAS, November 6, 2007; 104(45): 17753 - 17758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Barriere, C. Nemes, K. Du, and G. L. Lukacs Plasticity of Polyubiquitin Recognition as Lysosomal Targeting Signals by the Endosomal Sorting Machinery Mol. Biol. Cell, October 1, 2007; 18(10): 3952 - 3965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Obst, H.-M. van Santen, R. Melamed, A. O. Kamphorst, C. Benoist, and D. Mathis Sustained antigen presentation can promote an immunogenic T cell response, like dendritic cell activation PNAS, September 25, 2007; 104(39): 15460 - 15465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Herrmann, R. S. Agrawal, S. F. Connolly, R. L. McCaffrey, J. Schlomann, and D. J. Kusner MHC Class II levels and intracellular localization in human dendritic cells are regulated by calmodulin kinase II J. Leukoc. Biol., September 1, 2007; 82(3): 686 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Morokuma, N. Nakamura, A. Kato, M. Notoya, Y. Yamamoto, Y. Sakai, H. Fukuda, S. Yamashina, Y. Hirata, and S. Hirose MARCH-XI, a Novel Transmembrane Ubiquitin Ligase Implicated in Ubiquitin-dependent Protein Sorting in Developing Spermatids J. Biol. Chem., August 24, 2007; 282(34): 24806 - 24815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kuwano, C. M. Prazma, N. Yazawa, R. Watanabe, N. Ishiura, A. Kumanogoh, H. Okochi, K. Tamaki, M. Fujimoto, and T. F. Tedder CD83 influences cell-surface MHC class II expression on B cells and other antigen-presenting cells Int. Immunol., August 1, 2007; 19(8): 977 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Traub and G. L. Lukacs Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs J. Cell Sci., February 15, 2007; 120(4): 543 - 553. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
