I-2DNef-mediated downregulation of surface expression of HLA class I molecules and its effect on HIV-1-specific CTL escape of HIV-1

Nef-mediated downregulation of surface expression of HLA-A, B is widely known. And a report has shown that HIV-infected cells are able to evade CTL killing because of lack of antigen presentation to CTLs, due to HLA downregulation. But a number of CTLs are observed in patients with both acute and chronic HIV infection, suggesting that CTLs still recognize HIV antigens presented by HLA class I antigens. We, therefore, analyzed the effect of Nef-mediated HLA downregultion on T cell recognition by using HIV-specific CTL clones. The results of the analysis using CD4 T cells infected with HIV-1 with wild type Nef, with mutant Nef or lacking Nef protein provided evidence that the CTL failed to kill the targets due to HLA class 1 downregulation by Nef, while cytokine production showed a slight drop but still significant quantity. This indicates that CD8 T cells recognize HIV-1 epitopes presented by HLA class I molecules expressed on HIV-infected cell surface and that partial suppression of HIV virus replication is contributed largely to cytokine production rather than to killing of HIV-infected cells by CTL (J. Virol. 76:7535-7543, 2002). The study supports the fact that in HIV-1+ individuals, HIV-1 viral replication is not completely restrained despite presence of numerous HIV-specific CTLs.