Inhibitory effect of herpes simplex virus infection to target cells on recognition of minor histocompatibility antigens by cytotoxic T lymphocytes.
Target cell lysis by CTL specific for minor histocompatibility Ag (minor HA), which were generated in (C3H/He x BALB/c)F1 mice immunized with A/J mouse spleen cells, was dramatically reduced by infection of HSV to Neuro-2a (A/J mouse origin) cells as target. The reduction was apparent at 5 h after infection of HSV to target cells, when many viral proteins were produced in the cells. Conversely, MHC-restricted HSV-specific CTL-mediated cell lysis increased time dependently. Using an RNA virus, vesicular stomatitis virus, significant reduction of minor specific CTL-mediated target cell lysis was also found. During the time when this reduction of target cell lysis by HSV occurred, the surface expression of class I H-2Dd molecules was maintained, and anti-H-2a allo-MHC-specific CTL lysed HSV-infected Neuro-2a cells as strongly as uninfected Neuro-2a cells. When HSV-infected or uninfected Neuro-2a cells were treated with Brefeldin A that selectively blocks transportation of newly synthesized proteins out of endoplasmic reticulum, both HSV- and minor HA-specific CTL-mediated cell lyses were blocked. These observations demonstrated that minor HA are continuously synthesized and associated with class I molecules at pre-Golgi and transported via trans Golgi system with quick turnover, and that newly synthesized HSV Ag, which are also associated with class I molecules and transported via the same system, should take the place of intrinsic minor HA and be presented on the surface of the cells to be recognized by MHC-restricted CTL.
Kuzushima
K
K
Department of Immunology, Nagoya University School of Medicine, Japan.
Isobe
K
K
Morishima
T
T
Takatsuki
A
A
Nakashima
I
I
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D020126:Brefeldin A; D002451:Cell Compartmentation / Q000187:drug effects; D003517:Cyclopentanes / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology; D006561:Herpes Simplex / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000378:metabolism*; D007111:Immunity, Cellular; D051379:Mice; D008815:Mice, Inbred Strains; D008912:Minor Histocompatibility Loci / Q000276:immunology*; D011233:Precipitin Tests; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D003517:Cyclopentanes; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D020126:Brefeldin A