Adenovirus type 5 fiber knob binds to MHC class I α2 domain at the surface of human epithelial and B lymphoblastoid cells

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Abstract
Adenovirus serotype 5 (Ad5) fiber receptor was investigated using reverse antibody biopanning of a phage‐displayed hexapeptide library, and virus‐neutralizing monoclonal antibodies (mAbs 1D6.3 and 7A2.7) raised against recombinant Ad5 fiber knob. Both mAbs inhibited attachment of Ad5 to HeLa cells. Mimotopes of 1D6.3 showed homology with the C‐terminal segment of the α2 domain of the heavy chain of human MHC class I molecules (MHC‐I α2), and mimotopes of 7A2.7 were consensus to human fibronectin type III (FNIII) modules. In vitro, GST‐fused MHC‐I α2‐ and FNIII‐derived oligopeptides interacted with recombinant fibers in a subgroup‐specific manner. In vivo, the MHC–I α2 synthetic icosapeptide RAIVGFRVQWLRRYFVNGSR showed a net neutralization effect on Ad5 in HeLa cells, whereas the FNIII icosapeptide RHILWTPANTPAMGYLARVS significantly increased Ad5 binding to HeLa cells. Daudi cells, which lack surface expression of HLA class I molecules, showed a weak capacity for Ad5 binding. In β2‐microglobulin‐transfected Daudi cells, Ad5 attachment and permissivity were restored to HeLa cell levels, with 4000 receptors per cell and a binding constant of 1.4×1010/M. The results suggested that the conserved region of MHC‐I α2‐domain including Trp167 represents a high affinity receptor for Ad5 fiber knob, whereas ubiquitous FNIII modules would serve as auxiliary receptors.