Serum levels of several complement (C) components are controlled by genes linked to the major histocompatibility complex (MHC). The main objective of this proposal is to study the mechanism of action of these genes in the mouse. We will attempt to determine whether the genes which influence C levels (in particular C3) are structural or regulatory, and whether multiple genes have to be postulated. We will map them within the H-2 region and ascertain the importance of the non H-2 genetic background. Furthermore, the development of lymphoid organs, and perhaps of complement-receptor lymphocytes (CRL) are also under genetic control (HOM-1, CRL-1 genes). We propose to characterize the surface markers of the cells whose development is greatly influenced by H-2 genes, and to study the relationship between these genes and those which influence C levels. The present proposal is of relevance to the clarification of the biological function of the MHC and of the phylogeny and ontogeny of the immune system. The understanding of the mechanism of control of C3 levels in serum should also be of great interest in immunopathology, because of the multiple and key functions of C3 within the C cascade, in inflammation, in cell-mediated immunity, in phagocytosis, and perhaps in the immune response itself. BIBLIOGRAPHIC REFERENCES: Ferreira, A. and Nussenzweig, V. Control of C3 levels in mice during ontogeny by a gene in the central region of the H-2 complex. Nature, 260, 613, 1976. Ferreira, A., Fotino, M. and Nussenzweig, V. Relationship between 4a and 4b HLA-determined specificities and C3 receptors of leukocyte membrane. Eur. J. Immunol. In press, 1977.