The erythrocyte receptor for PfEBP-2 is GPC. (A) The receptor is neuraminidase- and trypsin-sensitive but chymotrypsin-resistant. ³⁵S-labeled proteins derived from parasite culture supernatants were mixed with red blood cells treated with neuraminidase (N), trypsin (T), or chymotrypsin (CT), or with untreated cells (WT). Separated cells were then lysed and the soluble fraction immunoprecipitated with anti–EBP2-3 antibodies. The immune complex was dissociated in SDS-PAGE buffer and run on 8% gels. The specific bound protein band in the autoradiograph corresponding to PfEBP-2 is shown. (B) PfEBP-2 does not bind to GPC null (Leach phenotype) cells. ³⁵S-labeled proteins were mixed with rare, variant red blood cells lacking GPB (S-s-), GPA [En(a-)], Kell (K₀), GPC (Leach), Dombrock [Gy(a-)], or control wild-type (WT) RBCs. The bound parasite ligand was immunoprecipitated with anti–EBP-2-3 antibodies. (C) PfEBP-2 binds differentially to GPC variant cells. Labeled proteins were mixed with identical amounts of Leach, Gerbich (Ge), Yus, or control (WT) RBCs. The bound parasite ligand was immunoprecipitated with anti–EBP-2-3 antibodies.