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Upregulated Expression of B-Cell Antigen Family Tandem Repeat Proteins by Leishmania Amastigotes

Author:
Goto, Yasuyuki, Carter, Darrick, Guderian, Jeffrey, Inoue, Noboru, Kawazu, Shin-Ichiro, Reed, Steven G.
Source:
Infection and immunity 2010 v.78 no.5 pp. 2138-2145
ISSN:
0019-9567
Subject:
B-lymphocytes, Leishmania infantum, Trypanosoma cruzi, amastigotes, antibodies, antigens, binding capacity, bioinformatics, enzyme-linked immunosorbent assay, gene expression regulation, hosts, mammals, parasites, parasitism, proteome, recombinant proteins, sequence homology, signal peptide
Abstract:
Proteins with tandem repeat (TR) domains have been found in various protozoan parasites, and they are often targets of B-cell responses. Through systematic analyses of whole proteomes, we recently demonstrated that two trypanosomatid parasites, Leishmania infantum and Trypanosoma cruzi, are rich in antigenic proteins with large TR domains. However, the reason that these proteins are antigenic was unclear. Here, by performing molecular, immunological, and bioinformatic characterizations of Leishmania TR proteins, we found two possible factors affecting the antigenicity of these proteins; one factor is their fundamental composition as TR proteins, and the other is regulation of their expression by parasites. Enzyme-linked immunosorbent assays (ELISAs) using recombinant proteins revealed that the copy number of the repeat affects the affinity of binding between antigens and antibodies, as expected based on thermodynamic binding kinetics. Other than containing TR domains, the TR proteins do not share characteristics, such as sequence similarity or biased cellular location predicted by the presence of a signal sequence(s) and/or a transmembrane domain(s). However, the TR proteome contained a higher percentage of proteins upregulated in amastigotes than the whole proteome, and upregulated expression of a TR protein seemed to affect its antigenicity. These results indicate that Leishmania parasites actively utilize the TR protein family for parasitism in mammalian hosts.
Agid:
284297