Adenovirus E3-19K Proteins of Different Serotypes and Subgroups Have Similar, Yet Distinct, Immunomodulatory Functions toward Major Histocompatibility Class I Molecules

• Published in: The Journal of biological chemistry 2011-05, Vol.286 (20), p.17631-17639
• Main Authors: Fu, Jie, Li, Lenong, Bouvier, Marlene
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenoviridae - immunology; Adenoviridae - metabolism; Adenovirus E3 Proteins - genetics; Adenovirus E3 Proteins - immunology; Adenovirus E3 Proteins - metabolism; Adenovirus Early Proteins - genetics; Adenovirus Early Proteins - immunology; Adenovirus Early Proteins - metabolism; Adenoviruses; Antigen Presentation; Cell Line; E3-19K; HLA-A Antigens - genetics; HLA-A Antigens - immunology; HLA-A Antigens - metabolism; HLA-B Antigens - genetics; HLA-B Antigens - immunology; HLA-B Antigens - metabolism; Humans; Immune Evasion Mechanisms; Immunology; Immunomodulatory Proteins; MHC; Protein Structure, Secondary; Species Specificity; Viral Protein
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M110.212050

Our understanding of the mechanism by which the E3-19K protein from adenovirus (Ad) targets major histocompatibility complex (MHC) class I molecules for retention in the endoplasmic reticulum is derived largely from studies of Ad serotype 2 (subgroup C). It is not well understood to what extent observations on the Ad2 E3-19K/MHC I association can be generalized to E3-19K proteins of other serotypes and subgroups. The low levels of amino acid sequence homology between E3-19K proteins suggest that these proteins are likely to manifest distinct MHC I binding properties. This information is important as the E3-19K/MHC I interaction is thought to play a critical role in enabling Ads to cause persistent infections. Here, we characterized interaction between E3-19K proteins of serotypes 7 and 35 (subgroup B), 5 (subgroup C), 37 (subgroup D), and 4 (subgroup E) and a panel of HLA-A, -B, and -C molecules using native gel, surface plasmon resonance (SPR), and flow cytometry. Results show that all E3-19K proteins exhibited allele specificity toward HLA-A and -B molecules; this was less evident for Ad37 E3-19K. The allele specificity for HLA-A molecules was remarkably similar for different serotypes of subgroup B as well as subgroup C. Interestingly, all E3-19K proteins characterized also exhibited MHC I locus specificity. Importantly, we show that Lys91 in the conserved region of Ad2 E3-19K targets the C terminus of the α2-helix (MHC residue 177) on MHC class I molecules. From our data, we propose a model of interaction between E3-19K and MHC class I molecules.