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Mol. Cells 2013; 36(5): 455-464

Published online November 30, 2013

https://doi.org/10.1007/s10059-013-0221-8

© The Korean Society for Molecular and Cellular Biology

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, and Taehoon Chun

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea, 1Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea, 2Department of Biomedical Laboratory Science, Gimcheon University, Gimcheon 740-704, Korea, 3Department of Life Sciences, College of Bionano, Gachon University, Seongnam 461-701, Korea, 4Department of Internal Medicine, College of Medicine, Seoul National University, Seoul 110-799, Korea

Received: August 5, 2013; Revised: September 6, 2013; Accepted: September 9, 2013

Abstract

To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-mem-brane 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 ?3 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

Article

Research Article

Mol. Cells 2013; 36(5): 455-464

Published online November 30, 2013 https://doi.org/10.1007/s10059-013-0221-8

Copyright © The Korean Society for Molecular and Cellular Biology.

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, and Taehoon Chun

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea, 1Research Institute and Hospital, National Cancer Center, Goyang 410-769, Korea, 2Department of Biomedical Laboratory Science, Gimcheon University, Gimcheon 740-704, Korea, 3Department of Life Sciences, College of Bionano, Gachon University, Seongnam 461-701, Korea, 4Department of Internal Medicine, College of Medicine, Seoul National University, Seoul 110-799, Korea

Received: August 5, 2013; Revised: September 6, 2013; Accepted: September 9, 2013

Abstract

To avoid host immune surveillance, human cytomegalovirus (HCMV) encoded endoplasmic reticulum (ER)-mem-brane 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 ?3 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

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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