NON-POLYMORPHIC ANTIGEN PRESENTATION MOLECULES 333 Spies, T., Morton, C.C., Nedespasov, S.A., Fiers, W., Pious, D. & Strominger, J.L. (1986X Genes for the tumor necrosis factor alpha and beta are linked to the human major histocompatibility complex. Proc. Nutl. Acud. Sci. USA, 83, 8699-8702. Spies, T. Bresnaban, M. & Strominger, J.L. (1989), Human major histocompatibility complex contains a mini- mum of 19 genes between the complement cluster and HLA-B. Proc. Nail. Acud. Sci. USA, 86, 8955-8958. Spies, T., Bresnahan, M., Bahram, S., Arnold, D., Blanck, G., Mellins, E., Pious, D. & DeMars, R. (1990), A gene in the human major histocompatibility complex class II region controlling the class I antigen presen- tation pathway. Nature (Land.), 348, 744747. TrowsdaIe, J. (1995), Both man and bird and beast: com- parative organization of MHC genes. immunogenet- ics, 41, l-17. Tsuji, K., Aizawa. M. & Sasazuki, RT. (1992), HLA 1991. Proceedings of the Eleventh International Histocom- patibility Workshop and Conference. Oxford Univer- sity Press. Van Kaer, L., Wu, M., lchikawa, Y., Ito, K., Bonneville, M., Ostrand-Rosenberg, S., Murphy, D.B. & Tone- gawa, S. (1991), Recognition of MHC TL gene prod- ucts by $!j T cells. Immunol. Rev., 120, 89-l 15. Vemet, C., Ribouchon, M-T., Chimini, G., Jouanolle A- M., SidibC, I. & Pontarotti, P. (1993), A novel coding sequence belonging to a new multicopy genefamily mapping within the human MHC class I region. immunogenetics, 38,47-53. Wolf, P.R. & Ploegh, H.L. (1995). How MHC class II molecules acquire peptide cargo : biosynthesis and trafficking through the endocytic pathway. Annu. Rev. Cell Dev. Biol., 11, 267-306. Zhou, Y. & Chaplin, D.D. (1993), Identification in the HLA class I region of a gene expressed late in kera- tinocyte differentiation. Proc. Natl. Acad. Sci- USA, 90, 9470-9474. The structure and evolution of FcRn N.E. Simister and J. Creighton Ahouse Rosenstiel Center for Basic Biomedical Sciences and Biology Department, Brandeis University, Waltham, MA 022.54-9110 (USA) Distribution and functions The neonatal Fc receptor (FcRn) was originally identified as the receptor responsible for IgG bind- ing to the intestinal epithelium of neonatal rats (Rodewald and Kraechenbuhl, 1984; Simister and Mostov, 1989; Simister and Rees, 1985). FcRn transports IgG from milk across the intestinal epi- thelial cells of the suckling (reviewed in Simister, 1990). This maternal IgG provides temporary pas- sive immunity during the period when the capacity to mount an affective antibody response is develo- ping (reviewed in Brambell, 1970), and also influences the development of the immunoglobulin repertoire (reviewed in Andrade et al., 1990). Subse- quently, FcRn was detected in other tissuesinvolved in the transmission of IgG from mother to young : rat foetal yolk sac (Roberts et aZ., 1990), mouse foetal yolk sac and neonatal intestine (Ahouse et al., 1993), and human placenta (Story et al., 1994), spe- cifically placental syncytiotrophoblast (N.E. Simis- ter et al., 1996). However, FcRn messenger RNA has been detected in many tissues of adult rats (Simister and Mostov, 1989) and humans (Story et Received May 2, 1996. al., 1994) and FcRn is present on adult rat hepato- cytes (Blumberg et al., 1995b). One function of FcRn in tissues that do not transport IgG, and beyond the perinatal period, appears to be to protect circulating IgG from degradation (E.J. Israel, D.F. Wilsker, K.C. Hayes, D. Schoenfeld and N.E. Simis- ter, submitted). Subunit composition FcRn contains two different polypeptide chains (Rodewald and Kraehenbuhl, 1984; Simister and Rees, 1985). An engineeredsoluble form of rat FcRn behaves as a single heterodimer on gel filtration (Gas- tine1 et al., 1992). In contrast, radiation target size analysis in situ in brush borders from neonatal rat intestinal epithelial cells gives a molecular mass corre- sponding to a dimer of FcRn heterodimers (hereafter FcRn dimers) @mister and Rees, 1983; 1985). Crys- tals of F&n and of FcRn!Fc complexes contain FcRn dimers (Burmeister et al., 1994a; 1994b). The physio- logical significance of F&n dimers is supported by the observation that dime&&ion is required for F&n