Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope analysis of anti-P0 autoantibodies in Chagas' disease patients.
Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by T. cruzi antigens sharing epitopes with host macromolecules has been implicated in the pathogenesis which is thought to have a significant autoimmune component. We report herein on the cloning and characterization of a full-length cDNA from a T. cruzi expression library encoding a protein, TcP0, that is homologous to the human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a clustering of residues that are evolutionarily conserved in higher eukaryotes. This includes an alanine- and glycine-rich region adjacent to a highly charged COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected individuals have antibodies reacting with host (self) P proteins, as well as with recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the reactivity of the T. cruzi infection sera with TcP0. This is similar to the specificity of anti-P autoantibodies described for a subset of patients with systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H. Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results suggest that T. cruzi P proteins may contribute to the development of autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of anti-P autoantibody may be similar in Chagas' and SLE patients. This study represents the first definitive report of the cloning of a full-length T. cruzi antigen that mimics a characterized host homologue in structure, function, and shared antigenicity.
Skeiky
Y A
YA
Seattle Biomedical Research Institute, Washington 98109.
Benson
D R
DR
Parsons
M
M
Elkon
K B
KB
Reed
S G
SG
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D014355:Chagas Disease / Q000276:immunology*; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015800:Protozoan Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D011817:Rabbits; D012269:Ribosomal Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D014349:Trypanosoma cruzi / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D010750:Phosphoproteins; D015800:Protozoan Proteins; D012269:Ribosomal Proteins; C054675:ribosomal protein P0