Immunochemical characterization of murine H-2 controlled Ss (serum substance) protein through identification of its human homologue as the fourth component of complement.

Abstract

The S region of the mouse H-2 complex is genetically defined by a series of alleles, or pseudoalleles, which control the level of a serum globulin, Ss, and of its allotypic variant, Slp. In contrast with the products of other genes in the complex, no homologue of the Ss protein has been found in other species, except the rat. In the present study, a component in human plasma was identifiedwhich cross-reacts with anti-mouse Ss, and which also displays electrophoretic and size similarities to the mouse Ss protein. This component was isolated and characterized immunochemical ly as the fourth component of human complement (C'4 or #1E globulin). Severa antisera monospecific for human C'4 cross-react with the mouse Ss protein and detect its genetically determined quantitative variations. The murine major histocompatibility complex (MHC), the H-2 complex, represents the most extensively studied segment of any mammalian chromosome. Many of the distinct products and functions governed by the H-2 complex in the mouse have been found to be controlled by a single circumscribed gene cluster in every species so far studied, suggesting a stringent evolutionary conservatism which has survived species divergence, at least from amphibia to man (1). The human HL-A and the murine H-2 complexes, though somewhat different in gene orders, display a marked similarity in composition. However, each complex includes loci for which no counterpart has yet been recognized in the other species. For instance, within the H-2 complex, approximately midway between the H-2K and the H-2D genes, which control transplantation antigens, is the Ss locus, which controls three as yet genetically inseparable polymorphisms involving the same serum ,B-globulin, the so-called Ss protein or serum substance (2-4). The traits concern a quantitative difference in the serum level of the Ss protein, presence or absence of a testosterone-dependent structural marker on the protein (Slp-sex-limited

Development of a hemolytic assay for mouse complement components in sera and the variation of their levels with age.

“…Recent work has made it clear that the Ss protein is an antigenic and structural homologue to human C4 (Curman et al 1975;Meo et al 1975;Carroll and Capra 1978;Ferreira et al 1978). However, in this study we observed no correlation of C4 activity with the Ss protein level in serum between Ss' and Ssl strains.…”

“…Recently, Lachmann et al (1975) and others (Curman et al 1975;Meo et al 1975;Carroll and Capra 1978;Ferreira et al 1978) reported that the Ss protein is mouse C4 molecule. The relationship between the amount of the Ss protein and C4 level in serum was examined in this experiment, and we could find a significant different result between males and females.…”

The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement.

“…Of the 13 propositi in whom no crossover was observed, meiosis was informative in only one parent and therefore a crossover is not ruled out in these children. An increase in intra-HLA recombinants has been observed in juvenile diabetes mellitus (42 (46)(47)(48). In addition, evidence has been presented that C3 level during ontogeny is MHC-linked in mouse (49).…”

A murine C4 molecule with reduced hemolytic efficiency.

“…Murine C2 was measured with an identical assay except for the substitution of C2-deficient human serum for the C4DGPS and an incubation time of 1 h. Antisera to Ss and Sip were prepared by standard methods that have been recently described (3,5,13). Goat antiserum to human factor B that cross-reacts with murine factor B was purchased from Atlantic Antibodies, Westbrook, Maine (5).…”