A comparison of the properties of two classes, C4A and C4B, of the human complement component C4.

Abstract

A remarkable difference has been observed between the reactivity of the two forms of human complement component C4. C4B binds twice as effectively as C4A to antibody‐coated red cells, but the reverse occurs with protein‐antigen complexes. C4B reacts much more effectively with hydroxyl groups than C4A and this is reversed for reaction with amino groups in spite of the very small difference in amino acid sequence between the two forms of C4. No other differences in stability, activation or inactivation were observed. These findings emphasise the biological advantage of the duplication of the C4 gene in its reaction with a wide range of antigenic structures. The correlation of the presence of different forms of C4 with susceptibility to autoimmune diseases may be explicable by these big differences in binding reactivity.

The effect of residue 1106 on the thioester‐mediated covalent binding reaction of human complement protein C4 and the monomeric rat α‐macroglobulin α1I3

“…C4b bound to sheep erythrocytes bearing activated C1 (EAC1) was detected with ~SI-labeled F(ab')2 fragments of rabbit anti-human C4 [6].…”

“…[3H]glycine and [3H]glycerol (Amersham) binding to C4 [12], and the pH dependence of binding [3,6], were performed as described previously. Rat C~ll3 was prepared according to [13] and human neutrophil elastase (HNE) was a gift from J. Travis.…”

“…They differ by only four amino acids within the sequence of six residues from position l l01 to 1106, but have very different binding properties. C4A, with the residues PCPVLD in the 1101-1106 hexapeptide, reacts efficiently with amino groups but poorly with hydroxyl groups, whereas C4B, with the sequence LSPVIH, reacts moderately with both nucleophilic groups [5][6][7][8]. Using site-directed mutagenesis at the cDNA level followed by expression of the modified proteins, it was found that the key residue lies in position 1106.…”

An integrated genomic analysis of gene-function correlation on schizophrenia susceptibility genes

“…C4A and C4B are highly polymorphic with variation at many residues, but the difference between their protein activities correlates with differences in only four amino acids. 60,61 It is therefore difficult to measure their concentration separately. 62 A significant increase in the frequency of homozygous C4B deficiency was found among Swedish patients with SZ compared with controls, 63 although others reported contradictory results.…”

Association of the complement allele c4aq0 with primary Sjögren's syndrome in japanese patients

“…Biochemical analysis of C4A and C4B proteins has revealed functional differences between C4A and C4B proteins. C4B is more active than C4A as determined by hemolytic assays, whereas C4A binds more effectively to immune complexes (22,23). These functional differences may indicate that C4A protein is directly involved in the pathogenesis of autoimmune diseases, including SS.…”