A comparison of viral immune escape strategies targeting the MHC class I assembly pathway.
Peptide fragments from proteins of intracellular pathogens such as viruses are displayed at the cell surface by MHC class I molecules thus enabling surveillance by cytotoxic T cells. Peptides are produced in the cytosol by proteasomal degradation and translocated into the endoplasmic reticulum by the peptide transporter TAP. Empty MHC class I molecules associate with TAP prior to their acquisition of peptides, a process which is assisted and controlled by a series of chaperones. The first part of this review summarizes our current knowledge of this assembly pathway and describes recent observations that tapasin functions as an endoplasmic reticulum retention molecule for empty MHC class I molecules. To defeat the presentation of virus-derived peptides, several DNA viruses have devised strategies to interfere with MHC class I assembly. Although these evasion strategies have evolved independently and differ mechanistically they often target the same step in this pathway. We compare escape mechanisms of different viruses with particular emphasis on the retention of newly synthesized MHC class I molecules in the endoplasmic reticulum and the inhibition of peptide transport by viral proteins.
R.W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA. kfrueh@prius.jnj.com
K
K
Früh
A
A
Gruhler
R M
RM
Krishna
G J
GJ
Schoenhals
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017920:Antiporters / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D026901:Membrane Transport Proteins; D010455:Peptides / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D014780:Viruses / Q000276:immunology*
D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; D014764:Viral Proteins; C107762:tapasin