F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement.
Trypanosoma cruzi calreticulin (TcCRT), described in our laboratory, retains several important functional features from its vertebrate homologues. We have shown that recombinant TcCRT inhibits the human complement system when it binds to the collagenous portion of C1q. The generation of classical pathway convertases and membrane attack complexes is thus strongly inhibited. In most T. cruzi-infected individuals, TcCRT is immunogenic and mediates the generation of specific antibodies. By reverting the C1q / TcCRT interaction, a parasite immune evasion strategy, these antibodies contribute to the host/parasite equilibrium. In an in vitro correlate of this situation, we show that the Clq/TcCRT interaction is inhibited by F(ab')2 polyclonal anti-TcCRT IgG fragments. It is therefore feasible that in infected humans anti-TcCRT antibodies participate in reverting an important parasite strategy aimed at inhibiting the classical complement pathway. Thus, membrane-bound TcCRT interacts with the collagenous portion Clq, and this Clq is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization. Based on our in vitro results, it could be proposed that the in vivo interaction between TcCRT and vertebrate Clq could be inhibited by F(ab')2 fragments anti-rTcCRT or against its S functional domain, thus interfering with the internalization process.
Aguilar
Lorena
L
Immunology Disciplinary Program, ICBM, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Ramírez
Galia
G
Valck
Carolina
C
Molina
María C
MC
Rojas
Alvaro
A
Schwaeble
Wilhelm
W
Ferreira
Viviana
V
Ferreira
Arturo
A
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D037282:Calreticulin / Q000502:physiology*; D015922:Complement C1q / Q000037:antagonists & inhibitors*; D005260:Female; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000502:physiology*; D011817:Rabbits; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D037282:Calreticulin; D007140:Immunoglobulin Fab Fragments; D015922:Complement C1q