CD1 antigen presentation by human dendritic cells as a target for herpes simplex virus immune evasion.
In contrast to MHC molecules, which present peptides, the CD1 molecules have been discovered to present lipid Ags to T cells. CD1-restricted T lymphocytes have been recently associated with resistance to virus infection. The mechanisms underlying activation of CD1-restricted T cells in the course of virus infection are not defined. In this study, we wanted to investigate the interaction of HSV with the antiviral CD1 Ag presentation system in human dendritic cells (DC). In response to low titers of HSV, the surface expression of CD1b and CD1d on human DC was up-regulated. These phenotypic changes enhanced the capacity of infected DC to stimulate proliferation of CD1-restricted T lymphocytes. High titers of HSV, however, lead to strong down-regulation of all surface CD1 molecules. This modulation of surface expression was associated with intracellular accumulation, colocalization with viral proteins, and disruption of the CD1 recycling machinery. Finally, even at low titers HSV interfered with the capacity of infected DC to stimulate the release of important cytokines by CD1d-restricted NKT cells. Thus, we demonstrate both the existence of a CD1 pathway allowing human DC to react to viral infection, as well as its blockage by a human herpesvirus.
Raftery
Martin J
MJ
Institute of Virology, Charité Medical School, Humboldt University Berlin, Schumannstrasse 20/21, D-10117 Berlin, Germany.
Winau
Florian
F
Kaufmann
Stefan H E
SH
Schaible
Ulrich E
UE
Schönrich
Günther
G
D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology* / Q000821:virology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008213:Lymphocyte Activation; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D014762:Viral Interference; D014764:Viral Proteins / Q000235:genetics
D018949:Antigens, CD1; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D014764:Viral Proteins