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Immunological Dominance of Trypanosoma cruzi Tandem Repeat Proteins

Goto, Yasuyuki, Carter, Darrick, Reed, Steven G.
Infection and immunity 2008 v.76 no.9 pp. 3967-3974
B-lymphocytes, Chagas disease, Trypanosoma cruzi, antigens, bioinformatics, consensus sequence, genes, immune response, parasites, pathogenicity, proteins, screening, sequence homology, signal peptide, surveys
Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, often acting as targets of B-cell responses. However, the extent of the repeats within Trypanosoma cruzi, the causative agent of Chagas' disease, has not been examined well. Here, we present a systematic survey of the TR genes found in T. cruzi, in comparison with other organisms. Although the characteristics of TR genes varied from organism to organism, the presence of genes having large TR domains was unique to the trypanosomatids examined, including T. cruzi. Sequence analyses of T. cruzi TR genes revealed their divergency; they do not share such characteristics as sequence similarity or biased cellular location predicted by the presence of a signal sequence or transmembrane domain(s). In contrast, T. cruzi TR proteins seemed to possess significant antigenicity. A number of previously characterized T. cruzi antigens were detected by this computational screening, and several of those antigens contained a large TR domain. Further analyses of the T. cruzi genome demonstrated that previously uncharacterized TR proteins in this organism may also be immunodominant. Taken together, T. cruzi is rich in large TR domain-containing proteins with immunological significance; it is worthwhile further analyzing such characteristics of TR proteins as the copy number and consensus sequence of the repeats to determine whether they might contribute to the biological variability of T. cruzi strains with regard to induced immunological responses, host susceptibility, disease outcomes, and pathogenicity.