The fourth component of routine complement (C4) is a ~200000 dalton glycoprotein that is synthesized as a single-chain intracellular precursor (pro-C4) and is subsequently cleaved to the e-,/%, and y-chains of native C4 (Roos et al. 1978, Parker et al. 1979, Fey et al. 1980). The molecular weights of the subunits are 98 000, 74 000, and 34 000 daltons, respectively. A size polymorphism exists in the murine C4 e-chain with some mouse strains producing C4 with 94 000 dalton e-chains due to" the lack of oligosaccharide (Parker et al. 1980 and Karp et al. 1982a). A hemolytically nonfunctional allotype of C4, sex-limited protein (Slp) is present in some strains (Passmore and Shreffler 1971). Slp is antigenically and structurally distinct from murine C4 having a larger e-chain and a smaller ?,-chain (Roos et al. 1978, Ferreira et al. 1978). Based on allelic differences among C4 and Slp molecules from intra-H-2 recombinant mice, the structural genes for these two proteins were mapped to the S region of H-2 (Parker et al. 1979, Carroll and Capra 1979, Parker et al. 1981, Ferreira et al. 1980a, 1980b).
In C4 or Slp preparations from mice bearing the S w7 region, a polypeptide with an M r of ~ 130000 was noted (Parker et al. 1979). These strains were employed for structural studies of C4 and Slp due to the fact that large amounts of both proteins are produced in peritoneal macrophage cultures from these mice. Recently, we have characterized these fragments as incompletely processed pro-C4 or pro-Slp molecules that contain the e and y-chains (Karp et al. 1982b).
To determine whether production of these aberrant C4 molecules having a/~, e+7 composition was a general phenomenon, or limited to S wv region products, peritoneal macrophages from various strains were cultured in the presence of 250 ~tCi/ml of [35S]-methionine and the C4 and Slp isolated by direct immunoprecipitation after the addition of carrier plasma (Parker et al. 1979). The