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The infective trypomastigote stage ofTrypanosoma cruzi expresses a set of surface glycoproteins that are known collectively as Tc85 and belong to the gp85/trans-sialidase supergene family. A member of this family, Tc85–11, with adhesive properties to laminin and cell surfaces was recently cloned. In this report, the Tc85–11 domain for cell binding and its corresponding receptor on epithelial cell LLC-MK₂are described. Using synthetic peptides corresponding to the Tc85–11 carboxyl-terminal segment, we show that the mammalian cell-binding domain colocalizes to the most conserved motif of the trypanosome gp85/trans-sialidase supergene family (VTVXNVFLYNR). Even though Tc85–11 binds to laminin, the 19-residue cell-binding peptide (peptide J) does not contain the laminin-binding site, because it does not bind to laminin or inhibit cell binding to this glycoprotein. The host cell receptor for the peptide was …