H-2 S region determined polymorphic variants of the C4, Slp, C2, and B complement proteins: a compilation.

Abstract

Until approximately 5 years ago, the murine complement system had largely been neglected, and most of the advances in the understanding of the structure-function relationships of the proteins of the complement pathways have been derived from studies with human and guinea pig proteins. The demonstration in the early 1970's that the mouse serum substance (Ss) protein was the homologue of the fourth component of human complement (C4) (reviewed by Shreffler 1976, Shreffler 1981, Shreffler et al. 1981) and the finding that the structural genes for C4, the second component of complement (C2), and a component of the alternative pathway (B), were in the human leukocyte antigen (HLA) complex markedly increased the interest in this area (reviewed by Alper 1981). In the middle 1970's, however, the problems of working with mouse complement seemed formidable in view of the relatively small quantities of starting materials, difficult and untested purification procedures, unstable components, and the lack of sensitive functional assays. Several unanticipated advances led to simple methods by which most of these problems could be bypassed and have permitted a majority of these studies to be performed. These advances have included: (1) the demonstration of biosynthesis of C4 (Roos et al. 1978), sex-limited protein (Slp) (Roos et al. 1978), and B (Bentley et al. 1976) by mouse peritoneal macrophages in shortterm in vitro cultures has allowed the incorporation into murine C4 of labeled amino acids (Roos et al. 1978) and sugars (Roos et al. 1980a); (2) the availability of labeled molecules has greatly facilitated structural studies, including the analysis of precursors (Parker et al. 1979) and their intracellular processing (Parker et al. 1979, Karp et al. 1982c), and of the secreted proteins. (3) Although widely applied to other H-2 molecules, purification of complement proteins by immunoprecipitation and analysis by SDS-PAGE gels had not previously been done. The advantages of these simple techniques, especially in the mouse, are enormous in that immunoprecipiration obviates the need for extensive purification procedures for each protein, and gel technology provides a powerful tool for examining structure (Roos et al. 1978, Ferreira et al. 1978). (4) Development of sensitive and specific hemolytic assays for