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挖掘麻风分枝杆菌的表面相关和分泌蛋白质组,以鉴定与免疫显性表位相关的疫苗和诊断标志物。

Excavating the surface-associated and secretory proteome of Mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.

作者信息

Rana Aarti, Thakur Shweta, Bhardwaj Nupur, Kumar Devender, Akhter Yusuf

机构信息

School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India.

School of Life Sciences, Central University of Himachal Pradesh, Shahpur, District-Kangra, Himachal Pradesh-176206, India

出版信息

Pathog Dis. 2016 Dec;74(9). doi: 10.1093/femspd/ftw110. Epub 2016 Nov 16.

Abstract

For centuries, Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs). Exploiting the known protein sequence and structural characteristics shared by the SASPs from bacteria, 17 lipoproteins, 11 secretory and 19 novel OMPs (including 4 essential proteins) were identified in M. leprae As OMPs represent the most exposed antigens on the cell surface, their immunoinformatics analysis showed that the identified 19 OMPs harbor T-cell MHC class I epitopes and class II epitopes against HLA-DR alleles (54), while 15 OMPs present potential T-cell class II epitopes against HLA-DQ alleles (6) and 7 OMPs possess T-cell class II epitopes against HLA-DP alleles (5) of humans. Additionally, 11 M. leprae OMPs were found to have B-cell epitopes and these may be considered as prime candidates for the development of new immunotherapeutics against M. leprae.

摘要

几个世纪以来,麻风病的病原体麻风分枝杆菌一直困扰着人类,尽管减毒活疫苗和抗生素已被广泛使用。表面相关蛋白和分泌蛋白是抗细菌的有吸引力的靶点。我们将生物学知识与计算方法相结合,对表面相关蛋白和分泌蛋白进行了全蛋白质组鉴定。我们还对免疫显性表位进行了计算分配,将其作为最重要的一类表面相关蛋白即外膜蛋白中潜在抗原候选物的坐标。利用细菌表面相关蛋白共有的已知蛋白质序列和结构特征,在麻风分枝杆菌中鉴定出17种脂蛋白、11种分泌蛋白和19种新型外膜蛋白(包括4种必需蛋白)。由于外膜蛋白是细胞表面最易暴露的抗原,其免疫信息学分析表明,鉴定出的19种外膜蛋白含有针对人类HLA - DR等位基因(54种)的T细胞MHC I类表位和II类表位,而15种外膜蛋白具有针对人类HLA - DQ等位基因(6种)的潜在T细胞II类表位,7种外膜蛋白具有针对人类HLA - DP等位基因(5种)的T细胞II类表位。此外,发现11种麻风分枝杆菌外膜蛋白具有B细胞表位,这些蛋白可被视为开发抗麻风分枝杆菌新免疫疗法的主要候选物。

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