title: Adenovirus E3-19K proteins of different serotypes and subgroups have similar, yet distinct, immunomodulatory functions toward major histocompatibility class I molecules.
abstract: 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 Lys(91) 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.
authors: Department of Microbiology and Immunology, University of Illinois, College of Medicine, Chicago, Illinois 60612, USA.
authors: Jie
authors: J
authors: Fu
authors: Lenong
authors: L
authors: Li
authors: Marlene
authors: M
authors: Bouvier
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017456:Adenovirus Early Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D017433:Protein Structure, Secondary; D013045:Species Specificity
chemical_list: D017503:Adenovirus E3 Proteins; D017456:Adenovirus Early Proteins; D015234:HLA-A Antigens; D015235:HLA-B Antigens