MOUSE MHC CLASS-I-LIKE FC-RECEPTOR ENCODED OUTSIDE THE MHC

In many mammalian species antibodies transmitted from the mother provi de humoral immunity to the young. Maternal IgG from milk is transporte d across the intestinal epithelium of neonatal rats by an Fc receptor (FcRn) that comprises an alpha-chain similar to the class I Ag of the MHC and beta2-microglobulin. Suckling mice also acquire antibodies by uptake from the gut. We made a neonatal mouse intestinal cDNA library and screened it with a probe encoding rat FcRn alpha-chain. The nucleo tide and predicted amino acid sequences of the two positive clones wer e very similar to those of rat FcRn. Comparison of the FcRn domains to various MHC class I and CD1 molecules suggests a divergence of FcRn f rom MHC early in the mammalian lineage. We expressed one of these cDNA in mouse 3T3 fibroblasts. Cells that expressed the cDNA product bound the Fc fragment of IgG with the same pH dependence as neonatal rat in testinal epithelium. We detected RNA that hybridize with the mouse cDN A only in neonatal small intestine and fetal yolk sac, two tissues inv olved in IgG transport. These data show that the mouse cDNA code for F cRn alpha-chain. The mouse Fc-Rn alpha-chain is similar in sequence to the class I MHC Ag, encoded on chromosome 17 in the mouse. However, w e find that the mouse FcRn gene lies outside the MHC, on chromosome 7.