Role for Major Histocompatibility Complex Class I in Regulating Natural Killer Cell-Mediated Killing of Virus-Infected Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 17; pp. 8337 - 8341
• Main Authors: Kaufman, Dan S., Schoon, Renee A., Leibson, Paul J.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.09.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antivirals; Biological and medical sciences; CD8 Antigens - immunology; Cell lines; Cellular biology; Cytotoxicity; Cytotoxicity, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Herpes Simplex - immunology; herpes simplex virus; Histocompatibility Antigens Class I - immunology; HLA antigens; Human herpesvirus 1; Humans; Immunity (Disease); Immunity, Cellular; Immunobiology; In Vitro Techniques; Infections; Killer Cells, Natural - immunology; Major Histocompatibility Complex; Medical research; Molecules; Natural killer cells; Organs and cells involved in the immune response; Simplexvirus; Simplexvirus - immunology; Viruses; Virus; Natural killer cell; Human; Infection; Cytotoxicity test; Herpesviridae; Major histocompatibility system; Alphaherpesvirinae; Cytotoxicity; Herpesvirus hominis; Immunofluorescence; Class I histocompatibility antigen
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.17.8337

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.