| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands; and
Institut National de la Sante et de la Recherche Medicale Unité 563, Centre de Physiopathologie Toulouse-Purpan, Hôpital Purpan, Toulouse, France
Human CMV (HCMV) can elude CTL as well as NK cells by modulating surface expression of MHC class I molecules. This strategy would be most efficient if the virus would selectively down-regulate viral Ag-presenting alleles, while at the same time preserving other alleles to act as inhibitors of NK cell activation. We focused on the HCMV unique short (US) region encoded protein US2, which binds to newly synthesized MHC class I H chains and supports their dislocation to the cytosol for subsequent degradation by proteasomes. We studied the effect of US2 on surface expression of individual class I locus products using flow cytometry. Our results were combined with crystal structure data of complexed US2/HLA-A2/
2-microglobulin and alignments of 948 HLA class I database sequences of the endoplasmic reticulum lumenal region inplicated in US2 binding. This study suggests that surface expression of all HLA-A and -G and most HLA-B alleles will be affected by US2. Several HLA-B alleles and all HLA-C and -E alleles are likely to be insensitive to US2-mediated degradation. We also found that the MHC class I endoplasmic reticulum-lumenal domain alone is not sufficient for degradation by US2, as illustrated by the stability of soluble HLA-G1 in the presence of US2. Furthermore, we showed that the membrane-bound HLA-G1 isoform, but also tailless HLA-A2, are targeted for degradation. This indicates that the cytoplasmic tail of the MHC class I H chain is not required for its dislocation to the cytosol by US2.
This article has been cited by other articles:
|
|
 |
|
  L. E. M. Oosten, D. Koppers-Lalic, E. Blokland, A. Mulder, M. E. Ressing, T. Mutis, A. G. S. van Halteren, E. J. H. J. Wiertz, and E. Goulmy TAP-inhibiting proteins US6, ICP47 and UL49.5 differentially affect minor and major histocompatibility antigen-specific recognition by cytotoxic T lymphocytes Int. Immunol., September 1, 2007; 19(9): 1115 - 1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. C. Hassink, M. T. Barel, S. B. Van Voorden, M. Kikkert, and E. J. Wiertz Ubiquitination of MHC Class I Heavy Chains Is Essential for Dislocation by Human Cytomegalovirus-encoded US2 but Not US11 J. Biol. Chem., October 6, 2006; 281(40): 30063 - 30071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Hegde, M. S. Chevalier, T. W. Wisner, M. C. Denton, K. Shire, L. Frappier, and D. C. Johnson The Role of BiP in Endoplasmic Reticulum-associated Degradation of Major Histocompatibility Complex Class I Heavy Chain Induced by Cytomegalovirus Proteins J. Biol. Chem., July 28, 2006; 281(30): 20910 - 20919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Thilo, P. Berglund, S. E. Applequist, J. W. Yewdell, H.-G. Ljunggren, and A. Achour Dissection of the Interaction of the Human Cytomegalovirus-derived US2 Protein with Major Histocompatibility Complex Class I Molecules: PROMINENT ROLE OF A SINGLE ARGININE RESIDUE IN HUMAN LEUKOCYTE ANTIGEN-A2 J. Biol. Chem., March 31, 2006; 281(13): 8950 - 8957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Barel, N. Pizzato, P. Le Bouteiller, E. J. H. J. Wiertz, and F. Lenfant Subtle sequence variation among MHC class I locus products greatly influences sensitivity to HCMV US2- and US11-mediated degradation Int. Immunol., January 1, 2006; 18(1): 173 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Le Bouteiller Human villous trophoblast and the lack of intron 4-retaining soluble HLA-G secretion: beware of possible methodological biases Mol. Hum. Reprod., October 1, 2005; 11(10): 711 - 713. [Full Text] [PDF]
|
|
|
|
|
|
J. LeMaoult, N. Rouas-Freiss, and E. D. Carosella HLA-G5 expression by trophoblast cells: the facts Mol. Hum. Reprod., October 1, 2005; 11(10): 719 - 722. [Full Text] [PDF]
|
|
|
|
 |
|
 N. T. Pande, C. Powers, K. Ahn, and K. Fruh Rhesus Cytomegalovirus Contains Functional Homologues of US2, US3, US6, and US11 J. Virol., May 1, 2005; 79(9): 5786 - 5798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Johansson, M. Johansson, E. Rosmaraki, G. Vahlne, R. Mehr, M. Salmon-Divon, F. Lemonnier, K. Karre, and P. Hoglund Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules J. Exp. Med., April 4, 2005; 201(7): 1145 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, R. Connors, M. R. Harris, T. H. Hansen, and L. Lybarger Requirements for the Selective Degradation of Endoplasmic Reticulum-Resident Major Histocompatibility Complex Class I Proteins by the Viral Immune Evasion Molecule mK3 J. Virol., April 1, 2005; 79(7): 4099 - 4108. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
