MHC-Linked Complement Components

Abstract

As our insights into the many and diverse roles of the major histo-compatibility complex (MHC) in immune functions have advanced, one very unexpected immunologic role has emerged — that of control of components of the complement system. Recognition of this function grew out of: 1. the definition of genetic variations in a specific mouse serum protein, the Ss (serum serological) trait, which became the primary genetic marker for the S region of the murine MHC — the H-2 complex (Shreffler and Owen, 1963); 2. the finding that significant differences in serum levels of total hemolytic complement in the mouse are controlled by the S region (Demant et al., 1973); and 3. the demonstration that the Ss protein is homologous to the fourth component (C4) of the classical human complement system (Meo et al., 1975; Curman et al., 1975 ; Lachman et al., 1975). The recognition by Demant et al. of H-2-associated differences in complement activity stimulated searches for asspciations of complement components with MHCs in other mammalian species, which were subsequently detected (cf. Alper, 1980). Evidence from man and the guinea pig clearly indicates control, by regions of the MHC, of at least two early components of the classical complement pathway, C2 and C4, and of Factor B of the alternative pathway. In the mouse, at least two other components of the complement system are MHC-linked. Clearly, the S region and its homologues in other species play an important role in fundamental immune mechanisms.