TRYPANOSOMA-CRUZI ACIDIC RIBOSOMAL P-PROTEIN GENE FAMILY - NOVEL P-PROTEINS ENCODING UNUSUAL CROSS-REACTIVE EPITOPES

We have cloned and characterized cDNA molecules that encode members of the acidic ribosomal protein family (TcP proteins) from the protozoan parasite Trypanosoma cruzi. These proteins have been shown to be anti genic in individuals with T. cruzi infection. Unlike other known eukar yotic cells, T. cruzi possesses at least four types of P protein genes TcP0, TcP1, TcP2a, and TcP2b, each of which is present in multiple co pies in the genome. These genes are present on at least three differen t chromosomes. Although the abundance of TcP0, TcP2a, and TcP2b transc ripts do not appear to vary among the parasite life-cycle stages, TcP1 is predominantly expressed in the epimastigote (insect) stage. TcP0 h as a C-terminal heptapeptide sequence that is similar to those of arch aebacterial acidic (P-like) proteins, but the TcP1/P2 proteins termina te with a shared sequence characteristic of the P proteins of higher e ukaryotes. The serine residues or other potential phosphorylation site s typically found within the highly charged C-terminal acidic domain a re absent in T. cruzi P proteins. Using synthetic peptides, we demonst rated that approximately 80% of T. cruzi-infected individuals produce two distinct but cross-reactive anti-P antibody specificities directed against the C-termini of TcP0 and TcP1/P2. We also expressed the full length (non-fusion) recombinant human PO and demonstrated that the T. cruzi anti-P antibodies cross-react with the C-terminal residues of h uman P-proteins. Conversely, human anti-P protein antibodies in sera f rom patients with SLE cross-react with the C-terminal epitope of T. cr uzi TcP1/P2 proteins. The cross-reactivity of anti-TcP antibodies with human P proteins suggests that, through antigenic conservation, TcP p roteins may contribute to the development of autoreactive antibodies i n Chagas' disease patients.