A seek-and-hide game between Cd1-restricted T cells and herpesviruses

Abstract

T and NK cells collaborate to control viral infections, discerning minute differences between infected and uninfected cells. At the same time, viruses have evolved to escape this discovery. In this issue of the JCI, Ganem and colleagues show that Kaposi sarcoma-associated herpesvirus (KSHV) inhibits CD1d presentation to T cells. This novel immune evasion strategy highlights the importance of CD1d-restricted T cells in controlling viral infection and raises an interesting question: how do T cells recognize viruses in the context of CD1 molecules that bind lipids? In the case of herpesviruses, alterations in endosomal trafficking might trigger redistribution of CD1/lipid complexes to cell surfaces, thereby promoting recognition by CD1d-restricted T cells.

Figure 1

Model for CD1-restricted recognition of herpesvirus infection. (A) Heterodimers of CD1 heavy chain and β₂m assemble with certain endogenous lipids (blue) in the ER and move through the Golgi apparatus to the cell surface. In normal cells, the majority of CD1 molecules accumulate in endosomes or lysosomes, where there is exchange of ER (or cell-surface) lipids with endosomal lipids (red). Following the acquisition of lipids, very few CD1 molecules return to the plasma membrane. Thus, CD1-restricted T cells that recognize bacterial or self lipids loaded in endosomes and/or lysosomes are not stimulated. Cell-surface CD1d molecules are internalized via clathrin-coated pits. (B) During herpesvirus infection there is assembly of virus particles and budding into TGN and endosomes. Following assembly, viral proteins promote substantial redistribution of TGN/endosomes and their contents to the plasma membrane. Mass movement of endosomes also relocalizes large amounts of CD1 with endosome-derived lipids to the cell surface. This could serve as a recognition signal that host cells are infected with a herpesviruses, causing CD1-restricted T cells to kill the target cell.