Antigenic crossreactivity of the alpha subunit of complement component C8 with the cysteine-rich domain shared by complement component C9 and low density lipoprotein receptor.
Complement component C9 contains two distinct cysteine-rich domains exhibiting high sequence resemblance to a domain present in the low density lipoprotein (LDL) receptor and epidermal growth factor precursor, respectively. Antibodies were raised against a peptide corresponding to the most conserved region of the LDL receptor/C9-homology segment. The antibodies were shown by immunoblotting to bind specifically to C9 but also to crossreact with C8 alpha, the alpha subunit of complement component C8. Moreover, a monoclonal antibody to a neoantigen present in polymerized C9 bound to an epitope exposed on C8 within the C5b-8 complex but buried in monomeric C8, suggesting that C8 and C9 undergo similar conformational changes during membrane-attack-complex assembly. Isolated C8 alpha-gamma exhibited the propensity to polymerize in the presence of Zn2+ and urea, as already demonstrated for C9. These data indicate that C8 alpha is closely related, both structurally and functionally, to C9.
D003185:Complement C8 / Q000276:immunology*; D003186:Complement C9 / Q000276:immunology*; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology; D003429:Cross Reactions; D003545:Cysteine; D000939:Epitopes; D006801:Humans; D046911:Macromolecular Substances; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011973:Receptors, LDL / Q000276:immunology*
D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D000939:Epitopes; D046911:Macromolecular Substances; D009842:Oligopeptides; D011973:Receptors, LDL; D003165:Complement System Proteins; D003545:Cysteine