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KMID : 0578320130360050455
Molecules and Cells
2013 Volume.36 No. 5 p.455 ~ p.464
Human Cytomegalovirus (HCMV) US2 Protein Interacts with Human CD1d (hCD1d) and Down-Regulates Invariant NKT (iNKT) Cell Activity
Han Ji-Hye

Rho Seung-Bae
Lee Jae-Yeon
Bae Joon-Beom
Park Se-Ho
Lee Suk-Jun
Lee Sang-Yeol
Ahn Curie
Kim Jae-Young
Chun Tae-Hoon
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 ¥á3 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.
KEYWORD
antigen presentation, HCMV US2 protein, human CD1d, human cytomegalovirus, invariant NKT cell
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