研究発表を行った学会；7th Asia-Oceania Histocompatibility Workshop and Conference
２００３年９月１６日〜１９日（Karuizawa, Japan）
タイトル；Effect of Nef-mediated HLA class I down-regulation on ability of HIV-1-specific CD8+ T cells to suppress HIV-1 replication
発表者；Mamoru Fujiwara
　　　（Division of Viral Immunology, Center for AIDS Research, Kumamoto University）
Abstract；
HIV-1-specific cytotoxic T lymphocytes (CTLs) are induced in acute and chronic phases of HIV-1 infection. However, CTLs cannot completely eliminate HIV-1 virus, and HIV-1-seropositive individuals develop AIDS if they are not treated with anti-retrovirus therapy. HIV-1Nef-mediated down-regulation of HLA-class I on the surface of HIV-1-infected cells is one of mechanisms that allow HIV-1 to evade CTLs. Previous studies showed that HIV-1-infected cells are hardly killed by HIV-1-specific CTLs due to Nef-mediated down-regulation of HLA-class I. In the present study, we investigated the ability of HLA-A*3303 CTL clones to inhibit HIV-1 replication by using a Nef-positive HIV-1 strain (NL-432) and a Nef-mutant HIV-1 strain (NL-M20A) that expresses a Nef protein which does not induce down-regulation of HLA class I molecules but is otherwise functional. Primary CD4+ T cells were incubated with the HIV-1 strains and co-cultured with five HIV-1-specific HLA-A*3303 CTL clones. The ability of HLA-A*3303 CTL clones to inhibit HIV-1 replication was investigated by measuring p24 expression in CD4+ cells by flow cytometry and p24 proteins in culture supernatant by ELISA. The results showed HIV-1-specific CTL clones suppressed replication of NL-M20A (about 70% suppression), while these CTL clones could partially suppress replication of NL-432 (10-40% suppression). In contrast, they failed to suppressed the replication of both viruses in HLA-mismatched cells infected with the viruses. These results suggest that HIV-1-specific CTLs partially recognize HIV-1 epitopes presented by HLA-A*3303 nevertheless the surface expression of HLA class I molecules are down-regulated by Nef.