Complement C2 receptor inhibitor trispanning and the β-chain of C4 share a binding site for complement C2

Jameel M. Inal, Jürg A. Schifferli

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36 Citations (Scopus)


Complement C2 receptor inhibitor trispanning (CRIT) of the Schistosoma parasite binds human C2 via the C2a segment. The receptor in vivo functions as C2 decoy receptor by directly competing with C4b for binding to C2. As a result, CRIT is able to limit the extent of classical pathway (CP) C3 convertase formation. We report that the CRIT-extracellular domain 1 (ed1) peptide inhibits CP-mediated complement activation with an ICH50 of ∼0.1 μM, the C-terminal 11 aa of CRIT-ed1, named H17, even more effectively. The β-chain region F222-Y232 of C4 shares 55% identity and 73% similarity with H17. Peptides based on this region also inhibit CP in a dose-dependent manner. As further evidence of C2 binding we showed CRIT-ed1 peptides and homologous C4 β-chain peptides to inhibit complement in C2 hemolytic assays. We have predicted C4 β-c F222-Y232 as a C2 binding site which we have termed the CRIT-ed1 domain, and the sequence [F/H]EVKX4/5P as a consensus C2-binding sequence. Anti-CRIT-ed1 cross-reacts with the C4 β-chain and F222EVKITPGKPY232 appears to be the key epitope recognized by this Ab. Furthermore, anti-CRIT-ed1 was found to inhibit CP activation in a total hemolytic assay. We believe that Schistosoma CRIT-ed1, as well as C4 β-chain peptides based on the CRIT-ed1 domain, function as interface peptides. These peptides, based on C2-binding sequences in CRIT, or C4, competitively inhibit the binding of C2 to C4b and thus limit the activation of C. The C4 peptides, unlike CRIT-ed1, did not inhibit the cleavage of C2 by C1s.

Original languageEnglish
Pages (from-to)5213-5221
Number of pages9
JournalJournal of Immunology
Issue number10
Publication statusPublished - 15 May 2002


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