This project aims at elucidating the role of major histocompatibility Class I antigen during embryonic development and in the maturation of the immune system. To this end we have studied the timing of Class I antigen expression in mouse embryogenesis throughout gestation, starting the egg cylinder stage by testing appearance of surface Class I antigens and of specifi mRNA. A low, but significant amount of mRNA was detected in embryos later that day 9 (early somite, heart beating stage): concordantly, the earliest surface Class I antigens were detected in day 10 embryos. Class I gene activity in embryos remained much lower than in the adult until the time of birth. These findings led us to conclude that Class I genes are developmentally regulated, and become active only after primordial organogenesis. Interferons (IFNs) were found to be capable of inducing Class I antigen in embryonic cells which otherwise do no have mRNA or surface antigens, suggesting a developmental role of interferon for MHC gene activation. Subsequently, a number of permanent cell lines has been established from mid somite stage embryos by transformation with a retrovirus (HaSV). These cells showed either a low or no Class I antigen expression, in agreement with characteristic observed in in vivo embryos. Further, these cells expressed a high level of the antigen upon treatment with IFN. In addition, undifferentiated embryonal carcinoma F9 cells representing very early embryos were found to respond to IFN. F9 cells normally express neither Class I message nor surface antigen; within 3 hours after addition of IFN, Class I specific mRNA becomes detectable. The majority of the cells display surface Class I antigen reaching at maximum 3 days after the treatment. Unlike retinoic acid which induces morphological differentiation as well, Class I antigens induction by IFN treatment is not accompained by cellular differentiation. These cells will be used as in vitro model system to study the mechanism of Class I gene activation.
