Modulation of MHC class I antigen presentation by the adenovirus E3-19K protein (100.8)

Abstract

Abstract The presentation of viral antigens by MHC I to CTLs is vital for elimination of infected cells. In turn, viruses have evolved various strategies to abrogate antiviral cellular immune responses. For example, the adenovirus (Ad) E3-19K protein retains MHC I in the endoplasmic reticulum, dramatically suppressing the cell-surface presentation of viral antigens. Many aspects of how E3-19K exerts its function towards MHC I are poorly understood. This knowledge is important as the E3-19K/MHC I interaction is thought to play a role in enabling Ads to cause persistent infections. We characterized biophysically and cellularly interaction between E3-19K proteins of different Ad serotypes (Ad 7 and 35, subgroup B; Ad 2 and Ad 5, subgroup C; Ad 37, subgroup D; and Ad 4, subgroup E) and HLA-A, -B, and -C molecules. Our results show that E3-19K proteins from Ad serotypes of the same subgroup display more similar binding properties for a given MHC I than those of different subgroups. Furthermore, E3-19K proteins exhibited allele- and locus-specificity; higher avidity for HLA-A relative to -B molecules, and no interaction with HLA-C molecules. FACS analysis showed that binding affinities correlated (in a negative way) with levels of MHC I expression on infected cells. Finally, we propose the first model of interaction between E3-19K and MHC I. Overall, our studies provide novel insights into the structure/function relationship of E3-19K and the molecular cell biology of antigen presentation.