Down-regulation of the class I HLA heterodimer and beta 2-microglobulin on the surface of cells infected with cytomegalovirus.
Cytotoxic T cell recognition of virus-infected cells requires the presentation of viral peptides by class I HLA molecules on the cell surface. We report here that cytomegalovirus (CMV) infection of human fibroblasts results in a progressive decrease in the cell surface expression of class I HLA and beta 2-microglobulin (beta 2m) such that in the late stages of infection the majority of infected cells have no detectable surface class I HLA. Coincident with decreased surface expression of class I HLA was an increase in his cytoplasmic expression. Confocal scanning laser microscopic analysis demonstrated that class I HLA and beta 2m accumulate in a perinuclear compartment inside the CMV-infected cell. Our data thus support the concept that CMV infection induces altered transport of class I HLA to the cell surface. We suggest that the virus has evolved this mechanism as a strategy to avoid T cell recognition of infected cells.
Barnes
P D
PD
Division of Communicable Diseases, Royal Free Hospital School of Medicine, London, U.K.
Grundy
J E
JE
D000954:Antigens, Surface / Q000302:isolation & purification / Q000378:metabolism*; D001692:Biological Transport; D002451:Cell Compartmentation; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism*; D015536:Down-Regulation; D005347:Fibroblasts; D005455:Fluorescent Antibody Technique; D006680:HLA Antigens / Q000302:isolation & purification / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin / Q000302:isolation & purification / Q000378:metabolism*
D000954:Antigens, Surface; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D001613:beta 2-Microglobulin