HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope

CTL recognize peptides that derive from viral protein Ags by proteolytic pr ocessing and are presented by MHC class I molecules. In this study we teste d whether coexpression of viral Ags in the same cell leads to competition b etween them. To this end, two L-d-restricted epitopes derived from HIV-1 en velope gp160 (ENV) and from CMV pp89 phosphoprotein were coexpressed. HIV E NV strain IIIB, but not MN variant, impaired recognition by specific CTL of CMV pp89 epitope 9pp89. Susceptibility to inhibition after ENV coexpressio n was inversely related to the amount of antigenic 9pp89 peptide processed from different antigenic constructs. In line with it, competition decreased the yield of naturally processed antigenic 9pp89 peptide bound to MHC clas s I molecules in coinfected cells. Also, point mutants of the presenting MH C class I molecule differed in their competition pattern. Collectively, the data imply that competition operates at the step of MHC-peptide complex as sembly or stabilization. We conclude that, although not the rule, in certai n combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele. These studies have implications for vaccine development and for understanding immunodominance .