HIV Type 1 Abrogates TAP-Mediated Transport of Antigenic Peptides Presented by MHC Class I

Abstract

Downregulation of MHC class I expression following human immunodeficiency virus 1 (HIV-1) infection is thought to play an important role in viral escape from immune recognition by cytotoxic T-lymphocytes(CTLs). Since exogenous addition of HIV-1-derived peptides restores susceptibility of HIV-1-infected cells to CTL-mediated lysis, we tested whether endogenous peptide loading is impaired in these cells. Our results show that in HIV-1-infected cells the ability of the transporter associated with antigen presentation (TAP) to translocate antigenic peptides from the cytosol to the lumen of the ER for presentation on MHC class I molecules is abolished. These data suggest that interference with the supply of antigenic peptides to the MHC class I pathway provides an additional mechanism by which HIV-1 evades the CTL-mediated immune response.