共查询到20条相似文献,搜索用时 46 毫秒
1.
An immunoinformatics approach to define T cell epitopes from polyketide and non‐ribosomal peptide synthesis proteins of Mycobacterium tuberculosis as potential vaccine candidates
下载免费PDF全文
![点击此处可从《Journal of molecular recognition : JMR》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The role of polyketide and non‐ribosomal proteins from the class of small molecule metabolism of Mycobacterium tuberculosis is well documented in envelope organization, virulence, and pathogenesis. Consequently, the identification of T cell epitopes from these proteins could serve to define potential antigens for the development of vaccines. Fourty‐one proteins from polyketide and non‐ribosomal peptide synthesis of small molecule metabolism proteins of M tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nanomeric peptides. All possible overlapping nanomeric peptide sequences from 41 small molecule metabolic proteins were generated through in silico and analyzed for their ability to bind to 33 alleles belonging to A, B, and C loci of HLA class I molecule. Polyketide and non‐ribosomal protein analyses revealed that 20% of generated peptides were predicted to bind HLA with halftime of dissociation T1/2 ≥ 100 minutes, and 77% of them were mono‐allelic in their binding. The structural bases for recognition of nanomers by different HLA molecules were studied by structural modeling of HLA class I‐peptide complexes. Pathogen peptides that could mimic as self‐peptides or partially self‐peptides in the host were excluded using a comparative study with the human proteome; thus, subunit or DNA vaccines will have more chance of success. 相似文献
2.
3.
The diagnostic potential of MPT63‐derived HLA‐A*0201‐restricted CD8+T‐cell epitopes for active pulmonary tuberculosis
下载免费PDF全文
![点击此处可从《Microbiology and immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Zhiliang Duan Dezhou Li Qingjun Jia Juanjuan Xu Xinyu Chen Zhigang Xu Huifang Liu Bokun Chen Jinsheng Wen 《Microbiology and immunology》2015,59(12):705-715
MPT63 protein is found only in Mycobacterium tuberculosis complex, including M. tuberculosis and M. bovis. Detection of MPT63‐specific IFN‐γ‐secreting T cells could be useful for the diagnosis of tuberculosis (TB) diseases. In the present study, the HLA‐A*0201 restriction of ten predicted MPT63‐derived CD8 + T‐cell epitopes was assessed on the basis of T2 cell line and HLA‐A*0201 transgenic mice. The diagnostic potential of immunogenic peptides in active pulmonary TB patients was evaluated using an IFN‐γ enzyme‐linked immunospot assay. It was found that five peptides bound to HLA‐A*0201 with high affinity, whereas the remaining peptides exhibited low affinity for HLA‐A*0201. Five immunogenic peptides (MPT6318–26, MPT6329–37, MPT6320–28, MPT635–14 and MPT6310–19) elicited large numbers of cytotoxic IFN‐γ‐secreting T cells in HLA‐A*0201 transgenic mice. Each of the five immunogenic peptides was recognized by peripheral blood mononuclear cells from 45% to 73% of 40 HLA‐A*0201 positive TB patients. The total diagnostic sensitivity of the five immunogenic peptides was higher than that of a T‐SPOT.TB assay (based on ESAT‐6 and CFP‐10) (93% versus 90%). It is noticeable that the diagnostic sensitivity of the combination of five immunogenic peptides and T‐SPOT.TB assay reached 100%. These MPT63‐derived HLA‐A*0201‐restricted CD8 + T‐cell epitopes would likely contribute to the immunological diagnosis of M. tuberculosis infection and may provide the components for designing an effective TB vaccine. 相似文献
4.
5.
Alistair K Brown Guoyu Meng Hemza Ghadbane David J Scott Lynn G Dover Jérôme Nigou Gurdyal S Besra Klaus Fütterer 《BMC structural biology》2007,7(1):55
Background
The cell wall of Mycobacterium tuberculosis contains a wide range of phosphatidyl inositol-based glycolipids that play critical structural roles and, in part, govern pathogen-host interactions. Synthesis of phosphatidyl inositol is dependent on free myo-inositol, generated through dephosphorylation of myo-inositol-1-phosphate by inositol monophosphatase (IMPase). Human IMPase, the putative target of lithium therapy, has been studied extensively, but the function of four IMPase-like genes in M. tuberculosis is unclear. 相似文献6.
Pavlenko M Roos AK Leder C Hansson LO Kiessling R Levitskaya E Pisa P 《Cancer immunology, immunotherapy : CII》2004,53(12):1085-1092
The ability of heat shock proteins (HSPs) to increase the potency of protein- and DNA-based vaccines has been previously reported. We have constructed several plasmid-based vectors encoding chimeric proteins containing prostate-specific antigen (PSA) fused to Mycobacterium tuberculosis hsp70, M. bovis hsp65, Escherichia coli DnaK (hsp70), or human hsp70. Immunizing mice with these plasmids induced CD8+ cytotoxic T lymphocytes (CTLs) specific to human PSA and protected mice from a subsequent subcutaneous challenge with PSA-expressing tumors. We did not observe a significant difference either in the levels of PSA-specific CTLs or in protection against tumor challenge in mice immunized with plasmids expressing PSA-HSP chimeric proteins, as compared to mice receiving a conventional PSA-expressing DNA plasmid. Our data indicate that using HSPs as fusion partners for tumor-specific antigens does not always result in the enhancement of antigen-specific CTL responses when applied in the form of DNA vaccines. 相似文献
7.
Antonia L. Pritchard Marcus L. Hastie Michelle Neller Jeffrey J. Gorman Chris W. Schmidt Nicholas K. Hayward 《Pigment cell & melanoma research》2015,28(3):281-294
Advancements in high‐resolution HPLC and mass spectrometry have reinvigorated the application of this technology to identify peptides eluted from immunopurified MHC class I molecules. Three melanoma cell lines were assessed using w6/32 isolation, peptide elution and HPLC purification; peptides were identified by mass spectrometry. A total of 13 829 peptides were identified; 83–87% of these were 8–11 mers. Only approximately 15% have been described before. Subcellular locations of the source proteins showed even sampling; mRNA expression and total protein length were predictive of the number of peptides detected from a single protein. HLA‐type binding prediction for 10 078 9/10 mer peptides assigned 88–95% to a patient‐specific HLA subtype, revealing a disparity in strength of predicted binding. HLA‐B*27‐specific isolation successfully identified some peptides not found using w6/32. Sixty peptides were selected for immune screening, based on source protein and predicted HLA binding; no new peptides recognized by antimelanoma T cells were discovered. Additionally, mass spectrometry was unable to identify several epitopes targeted ex vivo by one patient's T cells. 相似文献
8.
Elizabeth Fullam Akane Kawamura Helen Wilkinson Areej Abuhammad Isaac Westwood Edith Sim 《The protein journal》2009,28(6):281-293
Arylamine N-acetyltansferase (NAT) from Mycobacterium tuberculosis (TBNAT) is a potential drug target for anti-tubercular therapy. Recombinant TBNAT is much less soluble and is produced in
lower yields than the closely related NAT from Mycobacterium marinum (MMNAT). In order to explore MMNAT as a model for TBNAT in drug discovery, we compare the two mycobacterial NAT enzymes.
Two site-directed mutants of MMNAT have been prepared and characterised: MMNAT71, Tyr → Phe and MMNAT209, Met → Thr, in which
residues within 6 Å of the active-site cysteine have been replaced with the corresponding residue from TBNAT. Two chimeric
proteins have also been produced in which the third domain of MMNAT has been replaced by the third domain of TBNAT and vice
versa. The activity profile of the chimeric proteins suggests a role for the third domain in the evolutionary divergence of
NAT between these closely related mycobacterial species. 相似文献
9.
Background
The Mycobacterium tuberculosis 19-kDa lipoprotein has been reported to stimulate both T and B cell responses as well as induce a number of Th1 cytokines. In order to evaluate the Mycobacterium avium subsp. paratuberculosis (M. avium subsp. paratuberculosis) 19-kDa lipoprotein as an immunomodulator in cattle with Johne's disease, the gene encoding the 19-kDa protein (MAP0261c) was analyzed. 相似文献10.
11.
12.
Hiwa Målen Sharad Pathak Tina Søfteland Gustavo A de Souza Harald G Wiker 《BMC microbiology》2010,10(1):132
Background
Membrane- and membrane-associated proteins are important for the pathogenicity of bacteria. We have analysed the content of these proteins in virulent Mycobacterium tuberculosis H37Rv using Triton X-114 detergent-phase separation for extraction of lipophilic proteins, followed by their identification with high resolution mass spectrometry. 相似文献13.
The role of secretory proteins of Mycobacterium tuberculosis in pathogenesis and stimulation of specific host responses is well documented. They are also shown to activate different cell types, which subsequently present mycobacterial antigens to T cells. Therefore identification of T cell epitopes from this set of proteins may serve to define candidate antigens with vaccine potential. Fifty-two secretory proteins of M. tuberculosis H37Rv were analyzed computationally for the presence of HLA class I binding nonameric peptides. All possible overlapping nonameric peptide sequences from 52 secretory proteins were generated in silico and analyzed for their ability to bind to 33 alleles belonging to A, B and C loci of HLA class I. Fifteen percent of generated peptides are predicted to bind to HLA with halftime of dissociation T(1/2) >or=100 min and 73% of the peptides predicted to bind are mono-allelic in their binding. The structural basis for recognition of no-namers by different HLA molecules was studied employing structural modeling of HLA class I-peptide complexes and there exists a good correlation between structural analysis and binding prediction. Pathogen peptides that could behave as self- or partially self-peptides in the host were eliminated using a comparative study with the human proteome, thus reducing the number of peptides for analysis. The implications of the finding for vaccine development are discussed vis-à-vis the limitations of the use of subunit vaccine and DNA vaccine. 相似文献
14.
Olfa Frikha-Gargouri Radhouane Gdoura Abir Znazen Boutheina Gargouri Jalel Gargouri Ahmed Rebai Adnene Hammami 《BMC microbiology》2008,8(1):217
Background
The OmcB protein is one of the most immunogenic proteins in C. trachomatis and C. pneumoniae infections. This protein is highly conserved leading to serum cross reactivity between the various chlamydial species. Since previous studies based on recombinant proteins failed to identify a species specific immune response against the OmcB protein, this study evaluated an in silico predicted specific and immunogenic antigen from the OmcB protein for the serodiagnosis of C. trachomatis infections. 相似文献15.
Bosco Christiano Maciel da Silva Maria Fernanda Rios Grassi Raimundo Coutinho Rita Elizabeth Moreira Mascarenhas Viviana Nilla Olavarria Adriana Coutinho-Borgo Jorge Kalil Edecio Cunha Neto Simone Gon?alves Fonseca 《Memórias do Instituto Oswaldo Cruz》2014,109(8):999-1004
The interferon (IFN)-γ response to peptides can be a useful diagnostic marker of
Mycobacterium tuberculosis (MTB) latent infection. We identified promiscuous and
potentially protective CD4+ T-cell epitopes from the most conserved
regions of MTB antigenic proteins by scanning the MTB antigenic proteins GroEL2,
phosphate-binding protein 1 precursor and 19 kDa antigen with the TEPITOPE algorithm.
Seven peptide sequences predicted to bind to multiple human leukocyte antigen
(HLA)-DR molecules were synthesised and tested with IFN-γ enzyme-linked immunospot
(ELISPOT) assays using peripheral blood mononuclear cells (PBMCs) from 16 Mantoux
tuberculin skin test (TST)-positive and 16 TST-negative healthy donors. Eighty-eight
percent of TST-positive donors responded to at least one of the peptides, compared to
25% of TST-negative donors. Each individual peptide induced IFN-γ production by PBMCs
from at least 31% of the TST-positive donors. The magnitude of the response against
all peptides was 182 ± 230 x 106 IFN-γ spot forming cells (SFC) among
TST-positive donors and 36 ± 62 x 106 SFC among TST-negative donors (p =
0.007). The response to GroEL2 (463-477) was only observed in the TST-positive group.
This combination of novel MTB CD4 T-cell epitopes should be tested in a larger cohort
of individuals with latent tuberculosis (TB) to evaluate its potential to diagnose
latent TB and it may be included in ELISPOT-based IFN-γ assays to identify
individuals with this condition. 相似文献
16.
Michael Käser Simona Rondini Martin Naegeli Tim Stinear Francoise Portaels Ulrich Certa Gerd Pluschke 《BMC evolutionary biology》2007,7(1):177
Background
Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as Mycobacterium tuberculosis. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel) polymorphism among a diverse strain collection of Mycobacterium ulcerans, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs), comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within M. ulcerans, to define features of a hypothetical M. ulcerans most recent common ancestor and to confirm its origin from Mycobacterium marinum. 相似文献17.
Venkata Ravi Gutlapalli Aparna Sykam Anuraj Nayarisseri Sujai Suneetha Lavanya M Suneetha 《Bioinformation》2015,11(12):517-524
Mycobacterium tuberculosis is known to be associated with several autoimmune diseases such as systemic lupus erythematous,
rheumatoid arthritis and multiple sclerosis. This is attributed to sequence similarity between virulent factors and human proteins.
Therefore, it is of interest to identify such regions in the virulent factors to assess potential autoimmune related information. M.
tb specific virulent factors were downloaded from the VFDB database and its human homologs were identified using the sequence
comparison search tool BLASTP. Both virulent proteins and their corresponding human homologs were further scanned for
epitopes (B cell and HLA class I and II allele specific) using prediction programs (BCPRED and NETMHC). Data shows the
presence of matching 22 B-cell, 79 HLA class II and 16 HLA class I specific predicted epitopes in these virulent factors having
human homologs. A known peptide (HAFYLQYKNVKVDFA) associated with autoimmune atopic dermatitis is shown in the
superoxide dismutase homolog structures of the bacterium (PDB ID: 1IDS) and human (PDB ID: 2QKC). This data provides insight
into the understanding of infection-associated auto-immunity 相似文献
18.
Farahnaz Movahedzadeh Paul R Wheeler Premkumar Dinadayala Yossef Av-Gay Tanya Parish Mamadou Daffé Neil G Stoker 《BMC microbiology》2010,10(1):50
Background
Mycobacteria use inositol in phosphatidylinositol, for anchoring lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinosotol mannosides (PIMs) in the cell envelope, and for the production of mycothiol, which maintains the redox balance of the cell. Inositol is synthesized by conversion of glucose-6-phosphate to inositol-1-phosphate, followed by dephosphorylation by inositol monophosphate phosphatases (IMPases) to form myo-inositol. To gain insight into how Mycobacterium tuberculosis synthesises inositol we carried out genetic analysis of the four IMPase homologues that are present in the Mycobacterium tuberculosis genome. 相似文献19.
Shi‐Meng Zhang Hai‐Ping Dong Hui Wang Wei Luo Qian Wen Jian‐Chun He Xiao‐Fan Yang Li Ma 《Journal of cellular and molecular medicine》2016,20(9):1718-1728
New vaccines are needed to combat Mycobacterium tuberculosis (MTB) infections. The currently employed Bacillus Calmette‐Guérin vaccine is becoming ineffective, due in part to the emergence of multidrug‐resistant tuberculosis (MDR‐TB) strains and the reduced immune capacity in cases of HIV coinfection. CD8+ T cells play an important role in the protective immunity against MTB infections, and the identification of immunogenic CD8+ T cell epitopes specific for MTB is essential for the design of peptide‐based vaccines. To identify CD8+ T cell epitopes of MTB proteins, we screened a set of 94 MTB antigens for HLA class I A*11:01‐binding motifs. HLA‐A*11:01 is one of the most prevalent HLA molecules in Southeast Asians, and definition of T cell epitopes it can restrict would provide significant coverage for the Asian population. Peptides that bound with high affinity to purified HLA molecules were subsequently evaluated in functional assays to detect interferon‐γ release and CD8+ T cell proliferation in active pulmonary TB patients. We identified six novel epitopes, each derived from a unique MTB antigen, which were recognized by CD8+ T cells from active pulmonary TB patients. In addition, a significant level of epitope‐specific T cells could be detected ex vivo in peripheral blood mononuclear cells from active TB patients by an HLA‐A*11:01 dextramer carrying the peptide Rv3130c194‐204 (from the MTB triacylglycerol synthase Tgs1), which was the most frequently recognized epitope in our peptide library. In conclusion, this study identified six dominant CD8+ T cell epitopes that may be considered potential targets for subunit vaccines or diagnostic strategies against TB. 相似文献
20.
Na+/H+ antiporters are ubiquitous membrane proteins and play a central role in cell homeostasis including pH regulation, osmoregulation,
and Na+/Li+ tolerance in bacteria. The microbial communities in extremely hypersaline soil are an important resource for isolating Na+/H+ antiporter genes. A metagenomic library containing 35,700 clones was constructed by using genomic DNA obtained from the hypersaline
soil samples of Keke Salt Lake in Northwest of China. Two Na+/H+ antiporters, K1-NhaD, and K2-NhaD belonging to NhaD family, were screened and cloned from this metagenome by complementing
the triple mutant Escherichia coli strain KNabc (nhaA
−
, nhaB
−
, chaA
−) in medium containing 0.2 M NaCl. K1-NhaD and K2-NhaD have 75.5% identity at the predicted amino acid sequence. K1-NhaD has
78% identity with Na+/H+ antiporter NhaD from Halomonas elongate at the predicted amino acid sequence. The predicted K1-NhaD is a 53.5 kDa protein (487 amino acids) with 13 transmembrane
helices. K2-NhaD has 73% identity with Alkalimonas amylolytica NhaD. The predicted K2-NhaD is a 55 kDa protein (495 amino acids) with 12 transmembrane helices. Both K1-NhaD and K2-NhaD
could make the triple mutant E. coli KNabc (nhaA
−
, nhaB
−
, chaA−) grow in the LBK medium containing 0.2–0.6 M Na+ or with 0.05–0.4 M Li+. Everted membrane vesicles prepared from E. coli KNabc cells carrying K1-NhaD or K2-NhaD exhibited Na+/H+ and Li+/H+ antiporter activities which were pH-dependent with the highest activity at pH 9.5. Little K+/H+ antiporter activity was also detected in vesicles form E. coli KNabc carrying K1-NhaD or K2-NhaD. 相似文献