Neuronal cells are deficient in loading peptides onto MHC class I molecules.
Virally infected neurons avoid destruction by cytotoxic T lymphocytes (CTLs) by failing to express major histocompatibility complex (MHC) class I molecules. Like neurons in vivo and in primary culture, the OBL21 neuronal cell line expressed barely detectable levels of MHC class I molecules. This correlated with very low levels of mRNAs for the MHC class I heavy chains (alpha C). OBL21 cells also fail to provide MHC class I molecules with the peptides necessary for their efficient assembly and transport to the cell surface. This function can be restored by treatment with interferon-gamma (IFN-gamma). The mRNA for peptide transporters HAM1 and HAM2 was not detectable in OBL21 neuronal cells, but was induced by IFN-gamma treatment. Hence, the ability of neurons to evade CTL-mediated killing results from expression at low levels of the MHC class I alpha C, the peptide transporters HAM1 and HAM2, and possibly other genes of the peptide-loading machinery.
Joly
E
E
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Oldstone
M B
MB
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency*; D012333:RNA, Messenger / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D009479:Neuropeptides; D012333:RNA, Messenger