Allele- and locus-specific recognition of class I MHC molecules by the immunomodulatory E3-19K protein from adenovirus.
The E3-19K protein from human adenoviruses (Ads) retains class I MHC molecules in the endoplasmic reticulum. As a consequence, the cell surface expression of class I molecules is suppressed, allowing Ads to evade immune surveillance. Using native gel electrophoresis, gel filtration chromatography, and surface plasmon resonance, we show that a soluble form of the Ad type 2 (Ad2) E3-19K protein associates with HLA-A and -B molecules; equilibrium dissociation constants were in the nanomolar range and approximately 2.5-fold higher affinity for HLA-A (-A*0201, -A*0301, -A*1101, -A*3301, and -Aw*6801) relative to HLA-B (-B*0702 and -B*0801) molecules. Among the alleles of the HLA-A locus examined, HLA-A*3101 associated approximately 15-fold less avidly with soluble E3-19K. Soluble E3-19K interacted only very weakly with HLA-Cw*0304, and no interaction with HLA-Cw*0401 could be detected under identical conditions. Site-directed mutagenesis and flow cytometry demonstrated that MHC residue 56 plays a critical role in the association and endoplasmic reticulum retention of HLA-A molecules by E3-19K. This delineates the spatial environment around residue 56 as a putative E3-19K interaction surface on class I molecules. Overall, our data imply that a link may exist between host genetic factors and the susceptibility of individuals to Ad infections.
Liu
Hong
H
School of Pharmacy, University of Connecticut, 69 N. Eagleville Road, Storrs, CT 06269, USA.
Fu
Jie
J
Bouvier
Marlene
M
D000256:Adenoviridae / Q000276:immunology*; D017503:Adenovirus E3 Proteins / Q000276:immunology*; D000483:Alleles; D002462:Cell Membrane; D015234:HLA-A Antigens / Q000276:immunology; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic
D017503:Adenovirus E3 Proteins; D015234:HLA-A Antigens; C515740:HLA-A*11:01 antigen; D059870:HLA-A11 Antigen; D015791:HLA-A3 Antigen; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides