Intracellular traffic of the MHC class I-like IgG Fc receptor, FcRn, expressed in epithelial MDCK cells

Transfer of passive immunity from mother to the fetus or newborn involves t he transport of IgG across several epithelia, Depending on the species, IgG is transported prenatally across the placenta and yolk sac or is absorbed from colostrum and milk by the small intestine of the suckling newborn. In both cases apical to basolateral transepithelial transport of IgG is though t to be mediated by FcRn, an IgG Fc receptor with homology to MHC class I a ntigens. We have now expressed the human FcRn in polarized MDCK cells and a nalyzed the intracellular routing of the receptor. FcRn showed a predominan t intracellular localization at steady state. Newly synthesized FcRn was de livered in a non-vectorial fashion to both the apical and basolateral surfa ces of MDCK cell monolayers, Following internalization from the apical or b asolateral domain, the receptor transcytosed to the opposite surface. These findings provide direct evidence for the transepithelial transport functio n of FcRn and indicate that the receptor undergoes multiple rounds of trans cytosis.