title: Killing of human immunodeficiency virus-infected primary T-cell blasts by autologous natural killer cells is dependent on the ability of the virus to alter the expression of major histocompatibility complex class I molecules.
abstract: In the current study, we evaluated whether the capacity of HIV to modulate major histocompatibility complex (MHC) class I molecules has an impact on the ability of autologous natural killer (NK) cells to kill the HIV-infected cells. Analysis of HIV-infected T-cell blasts revealed that the decrease in MHC class I molecules on the infected cell surface was selective. HLA-A and -B were decreased on cells infected with HIV strains that could decrease MHC class I molecules, whereas HLA-C and -E remained on the surface. Blocking the interaction between HLA-C and -E and their corresponding inhibitory receptors increased NK cell killing of T-cell blasts infected with HIV strains that reduced MHC class I molecules. Moreover, we demonstrate that NK cells lacking HLA-C and -E inhibitory receptors kill T-cell blasts infected with HIV strains that decrease MHC class I molecules. In contrast, NK cells are incapable of destroying T-cell blasts infected with HIV strains that were unable to reduce MHC class I molecules. These findings suggest that NK cells lacking inhibitory receptors to HLA-C and -E kill HIV-infected CD4+ T cells, and they indicate that the capacity of NK cells to destroy HIV-infected cells depends on the ability of the virus to modulate MHC class I molecules.
authors.affiliation: Department of Microbiology and Immunology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Bonaparte
authors.forename: Edward
authors.initials: E
authors.lastname: Barker
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006678:HIV / Q000378:metabolism; D006679:HIV Seropositivity / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry; D015234:HLA-A Antigens / Q000737:chemistry; D015235:HLA-B Antigens / Q000737:chemistry; D015236:HLA-C Antigens / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008285:Major Histocompatibility Complex; D011971:Receptors, Immunologic / Q000737:chemistry; D054340:Receptors, KIR; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D013997:Time Factors; D000097625:HLA-E Antigens
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D000097625:HLA-E Antigens