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

Nature. 1999 Mar 4;398(6722):77-80. doi: 10.1038/18038.


Cytotoxic T lymphocytes (CTLs) are thought to detect viral infections by monitoring 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 proteins synthesized by the antigen-bearing cells. Macrophages and dendritic cells also have an alternative MHC class I pathway that can present peptides derived from extracellular antigens; however, the physiological role of this process is unclear. Here we show that virally infected non-haematopoietic cells are unable to stimulate primary CTL-mediated immunity directly. Instead, bone-marrow-derived cells are required as antigen-presenting cells (APCs) to initiate anti-viral CTL responses. In these APCs, the alternative (exogenous) MHC class I pathway is the obligatory mechanism for the initiation of CTL responses to viruses that infect only non-haematopoietic cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigen-Presenting Cells / immunology*
  • Antigens, Viral / immunology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / virology
  • Chimera
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / virology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Poliovirus
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccinia virus / immunology


  • Antigens, Viral
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Receptors, Virus
  • poliovirus receptor