Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity

Jihye Han; Seung Bae Rho; Jae Yeon Lee; Joonbeom Bae; Se Ho Park; Suk Jun Lee; Sang Yeol Lee; Curie Ahn; Jae Young Kim; Taehoon Chun

doi:10.1007/s10059-013-0221-8

Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity

Jihye Han, Seung Bae Rho, Jae Yeon Lee, Joonbeom Bae, Se Ho Park, Suk Jun Lee, Sang Yeol Lee, Curie Ahn, Jae Young Kim, Taehoon Chun

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

16 Citations (Scopus)

Abstract

To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and α3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells.

Original language	English
Pages (from-to)	455-464
Number of pages	10
Journal	Molecules and cells
Volume	36
Issue number	5
DOIs	https://doi.org/10.1007/s10059-013-0221-8
Publication status	Published - 2013 Nov

Bibliographical note

Funding Information:
This work was supported by Next-Generation BioGreen 21 program (No. PJ008089), Rural Development Administration, Republic of Korea, and a Korea University Grant (2012).

Keywords

Antigen presentation
HCMV US2 protein
Human CD1d
Human cytomegalovirus
Invariant NKT cell

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1007/s10059-013-0221-8

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title = "Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity",

abstract = "To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and α3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells.",

keywords = "Antigen presentation, HCMV US2 protein, Human CD1d, Human cytomegalovirus, Invariant NKT cell",

author = "Jihye Han and Rho, {Seung Bae} and Lee, {Jae Yeon} and Joonbeom Bae and Park, {Se Ho} and Lee, {Suk Jun} and Lee, {Sang Yeol} and Curie Ahn and Kim, {Jae Young} and Taehoon Chun",

note = "Funding Information: This work was supported by Next-Generation BioGreen 21 program (No. PJ008089), Rural Development Administration, Republic of Korea, and a Korea University Grant (2012).",

year = "2013",

month = nov,

doi = "10.1007/s10059-013-0221-8",

language = "English",

volume = "36",

pages = "455--464",

journal = "Molecules and cells",

issn = "1016-8478",

publisher = "Korean Society for Molecular and Cellular Biology",

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TY - JOUR

T1 - Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity

AU - Han, Jihye

AU - Rho, Seung Bae

AU - Lee, Jae Yeon

AU - Bae, Joonbeom

AU - Park, Se Ho

AU - Lee, Suk Jun

AU - Lee, Sang Yeol

AU - Ahn, Curie

AU - Kim, Jae Young

AU - Chun, Taehoon

N1 - Funding Information: This work was supported by Next-Generation BioGreen 21 program (No. PJ008089), Rural Development Administration, Republic of Korea, and a Korea University Grant (2012).

PY - 2013/11

Y1 - 2013/11

N2 - To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and α3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells.

AB - To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-membrane glycoprotein US2, which interferes with antigen presenting mechanism of major histocompatibility complex (MHC) class Ia and class II molecules. However, not many attempts have been made to study the effect of HCMV US2 on the expression of MHC class Ib molecules. In this study, we examined the effect of HCMV US2 on the expression and function of human CD1d (hCD1d), which presents glycolipid antigens to invariant NKT (iNKT) cells. Our results clearly showed that the physiological interaction between ER lumenal domain of HCMV US2 and α3 domain of hCD1d was observed within ER. Compared with mature form of hCD1d, immature form of hCD1d is more susceptible to ubiquitin-dependent proteasomal degradation mediated by HCMV US2. Moreover, the ectopic expression of HCMV US2 leads to the down-modulation of iNKT cell activity without significant change of hCD1d expression. These results will advance our understanding of the function of HCMV US2 in immune evasive mechanisms against anti-viral immunity of iNKT cells.

KW - Antigen presentation

KW - HCMV US2 protein

KW - Human CD1d

KW - Human cytomegalovirus

KW - Invariant NKT cell

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Human cytomegalovirus (HCMV) US2 protein interacts with human CD1d (hCD1d) and down-regulates invariant NKT (iNKT) cell activity

Abstract

Bibliographical note

Keywords

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