IDENTIFICATION OF AMINO-ACIDS WITHIN THE MHC MOLECULE IMPORTANT FOR THE INTERACTION WITH THE ADENOVIRUS PROTEIN E3 19K/

E3/19K protein of human adenovirus type 2 binds to class I MHC Ags the reby interfering with their cell surface expression and Ag presentatio n function. Currently, it is unclear exactly which structure of MHC mo lecules is recognized by the E3/19K protein. We have previously demons trated that the murine H-2 Kd Ag is able to associate with E3/19K, whe reas the allelic H-2K(k) molecule is not. By using exon shuffling betw een K-d and K-k molecules, the alpha 1 and alpha 2 domains of MHC clas s I molecules were identified as essential structures for binding the viral protein. In this report, we have examined the contribution oi in dividual amino acids within the alpha 2 domain of MHC for binding E3/1 9K. First, we show that within this domain the alpha-helical part is m ost important for the interaction with E3/19K. By using site-directed mutagenesis, Kd-specific amino acids were introduced into the alpha-he lix of the alpha 2 domain of K-k. By using the expression of mutageniz ed proteins in E3/19K(+) cells, we have identified Tyr 156 and Leu 180 as being essential for the association with the E3/19K protein. In ad dition, Kd residue Glu 163 seems to contribute to the complex formatio n. Furthermore, analysis of a panel of K-d/D-d recombinants indicates that a similar region in the D-d molecule, namely, the C-terminal half of the alpha 2 domain, affects binding to E3/19K. Combining these res ults with Ab binding data, we present two alternative models of how th e adenovirus protein may bind to the alpha 1 and alpha 2 domains.