Synthetic peptide-targeted selection of phage display mimotopes highlights immunogenic features of α-helical vs non-helical epitopes of Taenia solium paramyosin: implications for parasite- and host-protective roles of the protein.
Paramyosin of the pig-human parasite Taenia solium (TPmy) is a α-helical protein located on the worm surface that is suggested to fulfill an immunomodulatory role protecting the parasite against host immune system. Besides, in challenging experiments the protein shows a vaccine potential. These observations imply that TPmy harbors antigenic determinants for each of these contrasting actions. However the suggestion was not given a support from experimental data because respective epitopes have not been described thus far. To circumvent this difficulty, we use synthetic peptides with sequences of regions composed of α-helical or linear structure to induce rabbit antibody responses for phage-display mapping of epitope core amino-acid sets. Antibodies to α-helical regions were weak binders and M13 phage-displayed peptides selected by them from two different libraries exhibited no amino-acid similarities with the original protein site. In contrast, the antibodies produced in response to non-helical segment within α-helical structure were better binders and selectors of perfect structural mimics of the protein site. This first phage display epitope analysis of TPmy supports the notion that the rod-like α-helix, which encompasses over 90% of the total amino acids, may serve as an immunomodulatory shield that protects the parasite. Further, the seven non-helical segments of the TPmy molecule may represent the only anti-parasite discrete immunogenic epitopes whose representative mimotopes can be utilized in development of pure epitope vaccines.
Department of Molecular Biology and Biotechnology, Universidad Nacional Autónoma de México, Mexico. karlen@servidor.unam.mx
Karlen G
KG
Gazarian
Carlos F
CF
Solis
Tatiana G
TG
Gazarian
Merrill
M
Rowley
Juan P
JP
Laclette
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D017433:Protein Structure, Secondary; D013552:Swine; D041201:Taenia solium / Q000276:immunology* / Q000378:metabolism*; D014335:Tropomyosin / Q000737:chemistry / Q000276:immunology*
D000939:Epitopes; D019151:Peptide Library; D010455:Peptides; D014335:Tropomyosin