Role for major histocompatibility complex class I in regulating natural killer cell-mediated killing of virus-infected cells.
Target structures important for natural killer (NK) cell recognition of virally infected cells are not well defined. Since major histocompatibility complex (MHC) class I molecules bind viral peptides during acute infection, we evaluated whether an interaction between MHC and virus might influence the susceptibility of infected cells to NK cell-mediated lysis. To control for MHC class I expression on target cells, we used either HLA class I-deficient C1R cells or C1R sublines expressing transfected HLA class I gene products. Human NK cells were unable to preferentially lyse class I-deficient C1R cells after infection with herpes simplex virus (HSV). In contrast, HLA class I transfectants were significantly more susceptible to NK cell-mediated cytotoxicity after HSV infection. This occurred for HSV-infected C1R cells expressing any of the three HLA class I gene products tested (i.e., HLA-B27, HLA-A3, or HLA-Aw68), indicating that NK cell recognition in this system does not require "self" MHC and is not unique for a single haplotype. Productive HSV infection is required for the increased killing, since inoculation with UV-inactivated virus did not lead to increased lysis. In addition, since HSV infection of the transfectants did not significantly alter the level of class I expression, the change in susceptibility appears to be due to qualitative changes in the target structures on HSV-infected, HLA class I+ targets. These results demonstrate a role for MHC class I in regulating NK cell-mediated killing of virus-infected cells.
Kaufman
D S
DS
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905.
Schoon
R A
RA
Leibson
P J
PJ
D016827:CD8 Antigens / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006561:Herpes Simplex / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008285:Major Histocompatibility Complex; D018139:Simplexvirus / Q000276:immunology*
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I