The genetic control of quantitative (Ss) and qualitative (S1p) variations in two closely related mouse serum proteins has been localized to the S region of the mouse major histocompatibility complex (H-2). These serum proteins were found to be immunochemically and probably functionally homologous to human C4. Further biochemical and genetic characterizations of the Ss and S1p proteins have been done by immunoprecipitation techniques. Adherent peritoneal exudate cells from mice of strain B10.W7R, which express both the Ss and the S1p proteins, were cultured in vitro in medium containing 14C-labeled amino acids. These cells synthesized both Ss and S1p, as revealed by immunoprecipitation with anti-Ss and anti-S1p from the 14C-labeled, 24 hr macrophage culture supernatant. After SDS solubilization and 2-ME-reduction of the precipitates and separation on an SDS polyacrylamide slab gel, autoradiography revealed three major bands of activity with each antiserum. With anti-Ss, these polypeptides had m.w. of 98,000, 75,000, and 33,500, comparable to the α β and γ chains of human C4.

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