Association of human class I MHC alleles with the adenovirus E3/19K protein.
A panel of HLA-A and -B locus products was analyzed for their ability to associate with the adenovirus E3/19K (E19) protein in a co-immunoprecipitation assay. Three general categories of binding were identified. HLA-A2.1 and -B7 bind very well to E19. Compared with A2.1, 6- to 30-fold less E19 was associated with HLA-A3, -A1, and -Aw69; 50- to 150-fold less E19 was associated with HLA-Aw68, -B27, and -Bw58. Digestion with endoglycosidase H indicated that all levels of association resulted in inhibition of intracellular transport and processing, however, a fraction of Aw68, B27, and Bw58 escaped from intracellular retention. In contrast to the human class I molecules analyzed, transport of the murine H-2Dd molecule was not inhibited in the presence of E19. Hybrid class I molecules, in which exons encoding domains of A2.1 and H-2Dd had been exchanged, were used to define the regions of A2.1 required for E19 association. The alpha 1 and alpha 2 domains of A2.1 contain the minimum residues necessary for both stable association with E19 and subsequent inhibition of transport. A hybrid construct containing only the alpha 2 domain of A2.1 associated weakly with E19, but its post-translational processing was completely inhibited. In contrast, although a construct containing only the alpha 1 domain of A2.1 also associated weakly with E19, its intracellular transport was slowed rather than completely inhibited. Taken together, these results indicate that residues in both the alpha 1 and alpha 2 domains of A2.1 and Dd can influence stable binding of E19, with the phenotypic changes dominated by the origin of the alpha 2 domain.
Beier
D C
DC
Department of Microbiology, University of Virginia, Charlottesville 22908.
Cox
J H
JH
Vining
D R
DR
Cresswell
P
P
Engelhard
V H
VH
D017456:Adenovirus Early Proteins / Q000276:immunology* / Q000378:metabolism; D000260:Adenoviruses, Human / Q000276:immunology*; D000483:Alleles; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000737:chemistry; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011993:Recombinant Fusion Proteins
D017456:Adenovirus Early Proteins; D000956:Antigens, Viral; D006183:H-2 Antigens; D015234:HLA-A Antigens; D011993:Recombinant Fusion Proteins