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

Saw See Hong, Lucie Karayan, Jeannette Tournier, David T. Curiel, Pierre A. Boulanger

Research output: Contribution to journalArticlepeer-review

302 Scopus citations

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 x 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.

Original languageEnglish
Pages (from-to)2294-2306
Number of pages13
JournalEMBO Journal
Volume16
Issue number9
DOIs
StatePublished - May 1 1997

Keywords

  • Adenovirus serotype 5
  • Fiber knob
  • Fiber receptor
  • Fibronectin type III module
  • MHC class I heavy chain α2 domain

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