Prediction of Antigen Epitopes of Associated Protein Rv2004c Latent-infected by <i>Mycobacterium Tuberculosis</i>_Journal of Biomedical Engineering

Authors：

WANGDongfang ^1,2 , BAIXuejuan ² , LIUYinping ² , LIANGYan ² , WUXueqiong ² ,  LINMinggui ²

1. Hebei North University, Zhangjiakou 075000, China;
2. Institute for Tuberculosis Research, Army Tuberculosis Prevention and Control Key Laboratory, Beijng Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, the 309th Hospital of Chinese People's Liberation Army, Beijing 100091, China;

Corresponding author：

LINMinggui, Email: linminggui309301@126.com

Keywords：

Mycobacterium tuberculosis; Rv2004c; epitope prediction; bioinformatics

DOI：

10.7507/1001-5515.20160055

Video：

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To screen new tuberculosis diagnostic antigens and vaccine candidates, we predicted the epitopes of Mycobacterium tuberculosis latent infection-associated protein Rv2004c by means of bioinformatics. The homology between Rv2004c protein and human protein sequences was analyzed with BLAST method. The second structures, hydrophilicity, antigenicity, flexibility and surface probability of the protein were analyzed to predict B cell epitopes and T cell epitopes by Protean software of DNAStar software package. The Th epitopes were predicted by RANKPEP and SYFPEITHI supermotif method, the CTL epitopes were predicted by means of combination analyses of SYFPEITHI supermotif method, BIMAS quantitative motif method and NetCTL prediction method. The peptide sequences with higher scores were chosen as the candidate epitopes. Blast analysis showed that Rv2004c protein had low homology with human protein. This protein had abundant secondary structures through analysis of DNAStar software, the peptide segments with high index of hydrophilicity, antigenicity, surface probability and flexibility were widely distributed and were consistent with segments having beta turn or irregular coil. Ten candidates of B cell epitopes were predicted. The Th epitopes of Rv2004c protein were located after the 200th amino acid. Of 37 Th cell epitopes predicted, there were more epitopes of HLA-DRB1*0401 and HLA-DRB1*0701 phenotypes, and the MHC restrictive types of some Th cell epitopes exist cross overlap. Of 10 CTL epitopes predicted, there were more number and higher score of HLA-A2 restricted epitopes. Therefore Mycobacterium tuberculosis Rv2004c protein is a protein antigen with T cell and B cell epitopes, and is expected to be a new target protein candidate for tuberculosis diagnosis and vaccine.

Citation： WANGDongfang, BAIXuejuan, LIUYinping, LIANGYan, WUXueqiong, LINMinggui. Prediction of Antigen Epitopes of Associated Protein Rv2004c Latent-infected by Mycobacterium Tuberculosis. Journal of Biomedical Engineering, 2016, 33(2): 325-331. doi: 10.7507/1001-5515.20160055 Copy

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1. MURRAY C J, ORTBLAD K F, GUINOVART C, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013:a systematic analysis for the Global Burden of Disease Study 2013[J]. Lancet, 2014, 384(9947):1005-1070.
2. Centers for Disease Control and Prevention, USA[EB/OL].[2014-12-12]. http://www.cdc.gov/tb/publications/LTBI/intro.htm.
3. GERASIMOVA A, KAZAKOV A E, ARKIN A P, et al. Comparative genomics of the dormancy regulons in Mycobacteria[J]. J Bacteriol, 2011, 193(14):3446-3452.
4. FORERO M, PUENTES K, CORTES J, et al. Identifying putative Mycobacterium tuberculosis Rv2004c protein sequences that bind specifically to U937 macrophages and A549 epithelial cells[J]. Protein Science, 2005, 14(11):2767-2780.
5. HOZUMI H, TSUJIMURA K, YAMAMURA Y, et al. Immunogenicity of dormancy-related antigens in individuals infected with Mycobacterium tuberculosis in Japan[J]. Int J Tuberc Lung Dis, 2013, 17(6):818-824.
6. ZHAI M, CHEN F, ZHAO Y, et al. Novel epitopes identified from efflpumps of Mycobacterium tuberculosis could induce cytotoxic T lymphocyte response[J]. Peer J, 2015, 3:e1229.
7. 郭春艳, 赵向绒, 胡军.B细胞抗原表位的研究进展及其应用[J].生物技术通讯, 2013, 24(2):266-270.
8. 叶娟.结核分枝杆菌RD12区和RD5区特异性抗原的生物信息学分析及免疫原性初步评估[D].郑州:河南中医学院, 2014.
9. WANG Yanhua, WANG Guangxiang, OU Jiangtao, et al. Analyzing and identifying novel B cell epitopes within Toxoplasma gondii GRA4[J]. Parasites & Vectors, 2014, 7:474.
10. 李江英, 白雪娟, 梁艳, 等.用DNAStar软件预测Rv1410c结核分枝杆菌蛋白抗原表位[J].细胞与分子免疫学杂志, 2015, 31(4):474-477.
11. 刘银萍, 王全立, 张俊仙, 等.结核分枝杆菌Rv1419蛋白抗原表位的预测[J].中国防痨杂志, 2015, 37(1):52-55.
12. SLIGHT S R, RANGEL-MORENO J, GOPAL R, et al. CXCR5(+) T helper cells mediate protective immunity against tuberculosis[J]. J Clin Invest, 2013, 123(2):712-726.
13. PARIDA S K, POIRET T, LIU Zhenjiang, et al. T-Cell therapy:options for infectious diseases[J]. Clin Infect Dis, 2015, 61(Suppl 3):S217-S224.
14. PANIGADA M, STURNIOLO T, BESOZZI G, et al. Identification of a promiscuous T-cell epitope in Mycobacterium tuberculosis Mce proteins[J]. Infect Immun, 2002, 70(1):79-85.
15. NAIR S K, TOMARAS G D, SALES A P, et al. High-throughput identification and dendritic cell-based functional validation of MHC class Ⅰ-restricted Mycobacterium tuberculosis epitopes[J]. Sci Rep, 2014, 4:Article number:4632.
16. CHEN Fei, ZHAI Mingxia, ZHU Yuhuang, et al. In vitro and in vivo identification of a novel cytotoxic T lymphocyte epitope from Rv3425 of Mycobacterium tuberculosis[J]. Microbiol Immunol, 2012, 56(8):548-553.
17. ZHU Y H, GAO Y F, CHEN F, et al. Identification of novel T cell epitopes from efflux pumps of Mycobacterium tuberculosis[J]. Immunol Lett, 2011, 140(1-2):68-73.
18. 朱宇皇, 高艳锋, 吕虹, 等.结核分枝杆菌抗原Rv1258c、Rv1410c及Rv3425的HLA限制性CTL表位预测[J].郑州大学学报:医学版, 2011, 46(1):13-15.
19. SETTE A, SIDNEY J. Nine major HLA class Ⅰ supertypes account for the vast preponderance of HLA-A and-B polymorphism[J]. Immunogenetics, 1999, 50(3-4):201-212.
20. 白雪娟, 赵亚静, 梁艳, 等.结核潜伏感染蛋白Rv1737c B细胞、CTL及Th表位预测与分析[J].实用临床医药杂志, 2015, 19(3):5-9, 43.

Journal of Biomedical Engineering

Prediction of Antigen Epitopes of Associated Protein Rv2004c Latent-infected by Mycobacterium Tuberculosis

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