Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen

Cytotoxic T lymphocytes (CTLs) are thought to detect viral infections by mo nitoring the surface of all cells for the presence of viral peptides bound to major histocompatibility complex (MHC) class I molecules. In most cells, peptides presented by MHC class I molecules are derived exclusively from p roteins synthesized by the antigen-bearing cells'. Macrophages and dendriti c cells also have an alternative MHC class I pathway that can present pepti des derived from extracellular antigens; however, the physiological role of this process is unclear(2). Here we show that virally infected non-haemato poietic cells are unable to stimulate primary CTL-mediated immunity directl y. Instead, bone-marrow-derived cells are required as antigen-presenting ce lls (APCs) to initiate anti-viral CTL responses. In these APCs, the alterna tive (exogenous) MHC class I pathway is the obligatory mechanism for the in itiation of CTL responses to viruses that infect only non-haematopoietic ce lls.