Finding virus-infected cells
CD8+ T cells can detect CMV-infected cells, even though CMV interferes with MHC class I antigen presentation.
T cells seek and destroy cells containing viruses. They identify infected cells by the recognition of specialised proteins such as MHC class I molecules that display virus-derived proteins on the cell surface. But viruses like cytomegalovirus (CMV) disrupt the production of MHC class I molecules, thereby evading the T cell-mediated immune response. In March Nature Immunology, Veronika Groh and colleagues from the Fred Hutchinson Cancer Research Center, Seattle, propose a new mechanism by which CD8+ T cells detect CMV-infected cells even when few MHC class I molecules are present.
In addition to MHC class I molecules CD8+ T cells also express the receptor NKG2D that binds to the protein MIC. Working on cultured fibroblast and endothelial cells, Groh et al found a substantial increase in MIC expression in cells infected by CMV. MIC interaction with NKG2D increases T cell cytolytic and cytokine responses (Nat Immun 2001, 2:255-260). This could represent an important mechanism to circumvent viral interference with MHC class I antigen presentation. It will be important to determine if this strategy is involved in the detection of all virally infected cells or is specific for the detection of CMV.