Comparative immunogenicity and structural analysis of epitopes of different bacterial L-asparaginases

BMC Cancer

Research Article

Ilya N. Dyakov¹  Marat D. Kazanov²  Svetlana S. Aleksandrova³  Marina V. Pokrovskaya³  Vadim S. Pokrovsky⁴ 

[1] I.I. Mechnikov Research Institute of Vaccine and Sera, Moscow, Russia;Research and Training Center on Bioinformatics, A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Science, Moscow, Russia;V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, Russia;V.N. Orekhovich Institute of Biomedical Chemistry, Moscow, Russia;N.N. Blokhin Cancer Research Center, Moscow, Russia;

关键词: L-asparaginase;    Immunogenicity;    Epitope;   

DOI  :  10.1186/s12885-016-2125-4

 received in 2015-10-26, accepted in 2016-02-04,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundE.coli type II L-asparaginase is widely used for treatment of acute lymphoblastic leukemia. However, serious side effects such as allergic or hypersensitivity reactions are common for L-asparaginase treatment. Methods for minimizing immune response on L-asparaginase treatment in human include bioengeneering of less immunogenic version of the enzyme or utilizing the homologous enzymes of different origin. To rationalize these approaches we compared immunogenicity of L-asparaginases from five bacterial organisms and performed sequence-structure analysis of the presumable epitope regions.MethodsIgG and IgM immune response in C57B16 mice after immunization with Wollinella succinogenes type II (WsA), Yersinia pseudotuberculosis type II (YpA), Erwinia carotovora type II (EwA), and Rhodospirillum rubrum type I (RrA) and Escherichia coli type II (EcA) L-asparaginases was evaluated using standard ELISA method. The comparative bioinformatics analysis of structure and sequence of the bacterial L-asparaginases presumable epitope regions was performed.ResultsWe showed different immunogenic properties of five studied L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin as a second-line treatment. Studied L-asparaginases might be placed in the following order based on the immunogenicity level: YpA > RrA, WsA ≥ EwA > EcA. Most significant cross-immunogenicity was shown between EcA and YpA. We propose that a long N-terminus of YpA enzyme enriched with charged aminoacids and tryptophan could be a reason of higher immunogenicity of YpA in comparison with other considered enzymes. Although the recognized structural and sequence differences in putative epitope regions among five considered L-asparaginases does not fully explain experimental observation of the immunogenicity of the enzymes, the performed analysis set the foundation for further research in this direction.ConclusionsThe performed studies showed different immunogenic properties of L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin. The preferable enzymes for the second line treatment are WsA, RrA, or EwA.

【 授权许可】

CC BY   
© Pokrovsky et al. 2016