Regulation of CD1d expression and function by a herpesvirus infection
David Jesse Sanchez, Jenny E. Gumperz, Don Ganem
David Jesse Sanchez, Jenny E. Gumperz, Don Ganem
View: Text | PDF
Article Virology

Regulation of CD1d expression and function by a herpesvirus infection

Abstract

Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that the lytic replication cycle of the Kaposi sarcoma–associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This is caused by expression of the 2 modulator of immune recognition (MIR) proteins of the virus, each of which promotes the loss of surface CD1d expression following transfection into uninfected cells. Inhibition of CD1d surface expression is due to ubiquitination of the CD1d α-chain on a unique lysine residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated MHC class I downregulation, however, CD1d downregulation does not appear to include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d results in reduced activation of CD1d-restricted T cells in vitro. KSHV modulation of CD1d expression represents a strategy for viral evasion of innate host immune responses and implicates CD1d-restricted T cells as regulators of this viral infection.

Authors

David Jesse Sanchez, Jenny E. Gumperz, Don Ganem

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
MIR2 downregulation of CD1d is due to endocytosis but not enhanced degra...
MIR2 downregulation of CD1d is due to endocytosis but not enhanced degradation. (A) BJAB cells were transiently transfected with wild-type chimeric CD1d. Both panels show the level of chimeric CD1d when cotransfected with wild-type dynamin (solid black lines) as well as the level of CD1d antibody background cross-reactivity (dotted black lines). The gray lines represent chimeric CD1d levels in the presence of MIR2 and either wild-type (left panel) or dominant-negative dynamin (K44E, right panel). (B) The half-life of CD1d in BJAB cells expressing lacZ or MIR2 was analyzed by pulse chase. As shown, the presence of the MIR2 gene does not change the half-life of the CD1d chains. Chloroquine (C) was added to block lysosomal degradation and showed no effect. (C) The half-life of CD1d in HepG2 cells expressing lacZ or MIR2 were analyzed by pulse chase. As shown, the presence of the MIR2 gene does not change the half-life of the CD1d chains (left blots), but does increase the levels of degradation of MHC class I (right blots). Addition of chloroquine stopped the MHC class I degradation. (D) Total cellular levels of proteins in BJAB cells that were stable for expression of MIR2 or lacZ was determined by flow cytometry. The presence of the MIR2 gene did not change the total levels of CD1d, even though the surface levels of CD1d were decreased. This is in contrast to the decreased total and surface levels of B7.2 and MHC class I.