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-immunopr ecipitation 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 resul ted 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 th e murine H-2D(d) molecule was not inhibited in the presence of E19. Hy brid class I molecules, in which exons encoding domains of A2.1 and H- 2D(d) had been exchanged, were used to define the regions of A2.1 requ ired for E19 association. The alpha 1 and alpha 2 domains of A2.1 cont ain the minimum residues necessary for both stable association with E1 9 and subsequent inhibition of transport. A hybrid construct containin g only the alpha 2 domain of A2.1 associated weakly with E19, but its post-translational processing was completely inhibited. In contrast, a lthough a construct containing only the alpha 1 domain of A2.1 also as sociated weakly with E19, its intracellular transport was slowed rathe r than completely inhibited. Taken together, these results indicate th at residues in both the alpha 1 and alpha 2 domains of A2.1 and D-d ca n influence stable binding of E19, with the phenotypic changes dominat ed by the origin of the alpha 2 domain.