T-cell epitope

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Pathogenic Potential of Borna Disease Virus Lacking the Immunodominant CD8 T-Cell Epitope

Pathogenic Potential of Borna Disease Virus Lacking the Immunodominant CD8 T-Cell Epitope

mice is directed mainly against the epitope TELEISSI located in the viral nucleo- protein N, we generated BDV mutants that feature TQLEISSI in place of TELEISSI. We show that adoptive transfer of BDV N-specific CD8 T cells induced neurological disease in B10.BR mice persistently infected with wild-type BDV but not with the mutant virus expressing TQLEISSI. Surprisingly, the mutant virus replicated less well in adult MRL wild-type mice than in mutant mice lacking mature CD8 T cells. Furthermore, when MRL mice were infected with the TQLEISSI-expressing BDV mutant as newborns, neurological disease was observed, although at a lower rate and with slower kinetics than in mice infected with wild-type virus. These results confirm that TELEISSI is the major CD8 T-cell epitope in H-2 k
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Cloning, expression and T cell epitope prediction of fbpA and fbpB genes of Mycobacterium tuberculosis clinical isolates

Cloning, expression and T cell epitope prediction of fbpA and fbpB genes of Mycobacterium tuberculosis clinical isolates

The effective treatment and accurate diagnosis of tuberculosis (TB) are not established yet. The Bacillus Chalmette-Guerin vaccine did not provide significant results in the prevention of TB and had only 0-80% efficacy. The fbpA and fbpB genes of M. tuberculosis are antigenic proteins and considered to be virulence factors. They are capable of stimulating immune responses in TB patients. In this study, we observed cloning, expression and T-cell epitope prediction of fbpA and fbpB genes from clinical isolates. The isolates of MultiDrug-Resistant (MDR-TB) were cultured and extracted. The fresh Polymerase Chain Reaction (PCR) products of the fbpA and fbpB genes were inserted into pET SUMO plasmids and transformed into Escherichia coli BL21 (DE3), then expressed in LB medium induced by 1.0 µM of IPTG. Sample sequences were analyzed by ClustalW and NCBI BLAST programs. The T-cell epitope prediction was analyzed by GENETYX vers 8.0. The PCR results were 1071 bp (fbpA gene) and 978 bp (fbpB gene). The SDS-PAGE and Western blotting weighed 48-kDa (fbpA gene) and 46-kDa (fbpB gene). We obtained seven specific T-cell epitopes based on IAd Pattern Position on both genes. Based on Rothbard/Taylor Pattern Position, we discovered twenty-three and sixteen specific T-cell epitopes for fbpA and fbpB genes, respectively. The fbpA and fbpB genes that encode Ag85A and Ag85B proteins have epitopes that are recognized by lymphocyte T-cells and are potentially subunit TB vaccine candidates in the future.
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Characterization of T-cell response to woodchuck hepatitis virus core protein and protection of woodchucks from infection by immunization with peptides containing a T-cell epitope.

Characterization of T-cell response to woodchuck hepatitis virus core protein and protection of woodchucks from infection by immunization with peptides containing a T-cell epitope.

Specific activation of T cells appears to be a prerequisite for viral clearance during hepatitis B virus (HBV) infection. The T-cell response to HBV core protein is essential in determining an acute or chronic outcome of HBV infection, but how this immune response contributes to the course of infection remains unclear. This is due to results obtained from humans, which are restricted to phenomenological observations occurring during the clinical onset after HBV infection. Thus, a useful animal model is needed. Characterization of the T-cell response to the core protein (WHcAg) of woodchuck hepatitis virus (WHV) in woodchucks contributes to the understanding of these mechanisms. Therefore, we investigated the response of woodchuck peripheral blood mononuclear cells (PBMCs) to WHcAg and WHcAg-derived peptides, using our 5-bromo-2 * -deoxyuridine assay. We demonstrated WHcAg-specific proliferation of PBMCs and nylon wool-nonadherent cells from acutely WHV-infected woodchucks. Using a cross-reacting anti-human T-cell (CD3) antiserum, we identified nonadherent cells as woodchuck T cells. T-cell epitope mapping with overlapping peptides, covering the entire WHcAg, revealed T-cell responses of acutely WHV-infected woodchucks to peptide 1–20 , peptide 100–119 , and
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T Cell Epitope Clustering in the Highly Immunogenic BZLF1 Antigen of Epstein-Barr Virus

T Cell Epitope Clustering in the Highly Immunogenic BZLF1 Antigen of Epstein-Barr Virus

Why are some regions of the BZLF1 sequence so rich in CD8 ⫹ T cell epitopes while other areas are not targeted at all? One pos- sibility is that sequence similarity with human protein sequences results in immune tolerance to parts of the BZLF1 antigen. Several previous studies have shown the phenomenon of epitope cluster- ing. Examples range from bacteria and tumor antigens to HIV. Kim and DeMars found that the major outer membrane protein of Chlamydia trachomatis displays a coclustering of class I and class II epitopes within a 20-mer region of the protein (30). Fur- thermore, Valmori and colleagues identified clusters of closely overlapping epitopes in the NY-ESO-1 protein (expressed in sev- eral types of tumors) (31). HIV studies have shown epitope clus- tering in the Nef and Gag proteins, corresponding to areas of protein hydrophobicity. Interestingly, CD8 ⫹ T cell epitopes are predicted to be quite evenly distributed throughout the BZLF1 sequence according to the Immune Epitope Analysis Resource (http://tools.immuneepitope.org/main/) for 10 common HLA class I alleles (data not shown), which uses predictors of protea- somal processing, TAP transport, and MHC binding to produce an overall score for each peptide’s intrinsic potential for being a T cell epitope.
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Loss of Immunization-Induced Epitope-Specific CD4 T-Cell Response following Anaplasma marginale Infection Requires Presence of the T-Cell Epitope on the Pathogen and Is Not Associated with an Increase in Lymphocytes Expressing Known Regulatory Cell Phenot

Loss of Immunization-Induced Epitope-Specific CD4 T-Cell Response following Anaplasma marginale Infection Requires Presence of the T-Cell Epitope on the Pathogen and Is Not Associated with an Increase in Lymphocytes Expressing Known Regulatory Cell Phenotypes

We have shown that in cattle previously immunized with outer membrane proteins, infection with Anaplasma marginale in- duces a functionally exhausted CD4 T-cell response to the A. marginale immunogen. Furthermore, T-cell responses following infection in nonimmunized cattle had a delayed onset and were sporadic and transient during persistent infection. The induc- tion of an exhausted T-cell response following infection presumably facilitates pathogen persistence. In the current study, we hypothesized that the loss of epitope-specific T-cell responses requires the presence of the immunizing epitope on the pathogen, and T-cell dysfunction correlates with the appearance of regulatory T cells. In limited studies in cattle, regulatory T cells have been shown to belong to ␥␦ T-cell subsets rather than be CD4 T cells expressing forkhead box protein P3 (FoxP3). Cattle ex- pressing the DRB3*1101 haplotype were immunized with a truncated A. marginale major surface protein (MSP) 1a that contains a DRB3*1101-restricted CD4 T-cell epitope, F2-5B. Cattle either remained unchallenged or were challenged with A. marginale bacteria that express the epitope or with A. marginale subsp. centrale that do not. Peripheral blood and spleen mononuclear cells were monitored for MSP1a epitope F2-5B-specfic T-cell proliferative responses and were stained for ␥␦ T-cell subsets or CD4 ⴙ CD25 ⴙ FoxP3 ⴙ T cells before and during infection. As hypothesized, the induction of T-cell exhaustion occurred only following infection with A. marginale, which did not correlate with an increase in either CD4 ⴙ CD25 ⴙ FoxP3 ⴙ T cells or any ␥␦ T-cell sub- set examined.
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Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1.

Identification of a T-cell epitope adjacent to neutralization antigenic site 1 of poliovirus type 1.

Immunization of BALB/c H-2d mice with the uncoupled p86-115 peptide, which represents VP1 amino acids 86 to 115 and contains both the T-cell epitope and the C3 neutralization epitope, in[r]

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T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+ Donors

T Cell Epitope Mapping of JC Polyoma Virus-Encoded Proteome Reveals Reduced T Cell Responses in HLA-DRB1*04:01+ Donors

FIG 1 JCV genome organization, protein sequence variability, and mapping of peptide pools. (A) The genomic organization of the JCV reference genome (NC_001699), consisting of 5,130 bp, is shown with the nucleotide positions of all open reading frames indicated by colored arrows. Nucleotides are numbered relative to the JCV reference genome (NC_001699). Large T antigen (LTAg, dark blue arrow), small T antigen (STAg, light blue arrow), three additional alternative splice variants of the large T antigen (T=135, T=136, and T=165, dark blue arrows), agnoprotein (agno, red arrow), VP1 (dark green arrow), VP2 (light green arrow), and VP3 (orange arrow) are shown, as well as early and late mRNAs (gray, dotted arrows), the tandem repeats (TR, gray boxes) in the noncoding region (NCR, gray line), and JCV microRNA (miRNA) (miR-J1, black dot). Introns within the respective open reading frames are depicted as boxes with dashed lines. (B) Sequence variability of amino acid sequences among different JCV strains (continuous line) and among nine human PyVs (dashed line) comprised of BKV (accession number NC_001538), JCV (NC_001699), KIV (NC_009238), WUV (NC_009539), MCV (NC_010277), HPyV6 (NC_014406), HPyV7 (NC_014407), TSV (NC_014361), and HPyV9 (NC_015150). Similarity scores were plotted against the respective amino acid of each protein and matched to the relative nucleotide position of the JCV reference genome (NC_001699). (C) Mapping of 42 peptide pools (colored boxes) to the relative nucleotide positions of the JCV reference genome (NC_001699). LTAg, STAg, T=135, T=136, and T=165, agno, VP1, VP2, and VP3 (gray-shaded boxes) are shown, as well as early and late mRNAs (black lines) including introns (dashed lines) and polyadenylated 3= ends [3= (A)n], in relation to the JCV reference genome (NC_001699). Each pool consists of 5 different peptides. A total of 169 peptides overlap by 5 amino acids (pep; nonhatched boxes), and 35 peptides contain single amino acid substitutions
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Identification of a T cell epitope in the Staphylococcus aureus Panton Valentine LukS PV component

Identification of a T cell epitope in the Staphylococcus aureus Panton Valentine LukS PV component

challenged with peptides 7 (149 - 173), 8 (169 - 193) or 14 (289 - 312) elicited significant responses compared to footpad swelling measurements observed following challenge with the remaining peptides, however, re- sponses observed following challenge with either peptide 7 (149 - 173), 8 (169 - 193) or 14 (289 - 312) were sig- nificantly below the response elicited following chal- lenge with LukS-PV (Figure 2(a)). Interestingly, in vitro stimulation of the L S T cell line with the peptide panel did

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Three-Dimensional Structure Determines the Pattern of CD4+ T-Cell Epitope Dominance in Influenza Virus Hemagglutinin

Three-Dimensional Structure Determines the Pattern of CD4+ T-Cell Epitope Dominance in Influenza Virus Hemagglutinin

(less than 6%), weak (6 to 24%), moderate (25 to 60%), or strong (greater than 60%). In the present work, peptides were assigned scores corresponding to the average response for the range: negative (3%), weak (15%), moderate (43%), or strong (81%). Res- idues that appeared in multiple peptides were assigned the average of the scores. (ii) Phl p 1. The responses of T-cell lines or clones from nine allergic patients reported by Schenk et al. (59) were based on proliferation stimulated by 12-mer peptides spanning Phl p 1 with nine-residue overlaps. The authors scored the response for a given clone as positive if the SI was greater than 10. Epitope scores were assigned to residues according to the number of patients whose lines or clones responded to the peptide that contained the residue. The profile of raw epitope scores was smoothed with a seven-residue moving window average. The first-derivative profile generated as described for HA was smoothed with a seven-residue moving window average. Dominance peaks were assigned as for HA.
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Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes.

Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes.

Strikingly, the lymphocytes of all 4 donors responded primarily to a region defined by a single peptide spanning residues 338 to 355, and the lymphocytes of 2 donors responded to an over[r]

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Influenza T-cell Epitope-Loaded Virosomes Adjuvanted with CpG as a Potential Influenza Vaccine

Influenza T-cell Epitope-Loaded Virosomes Adjuvanted with CpG as a Potential Influenza Vaccine

these antibodies are usually not cross-reactive, they do provide protection against homologous influenza strains. Thus, in case the circulating virus matches the source influenza strain of the virosomes, additional humoral responses can aid in protec- tion. CpG adjuvanted P-V induced significantly (p <0.01) higher HI titers compared to non-adjuvanted P-V (Fig. 3e). Total IgG titers showed a similar significant (p<0.05) increase after addition of CpG to the P-V (Supplementary Figure S1C). This underlines that CpG is not only an effective adjuvant for T-cell induction, but also im- proves B-cell responses, as observed previously (12). As expected, there were no detectable HI and total IgG titers in sera of control mice receiving PBS or peptide mixed with IFA and CpG, due to the lack of influenza surface antigens in these formulations.
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Identification of the Immunodominant H-2Kk-Restricted Cytotoxic T-Cell Epitope in the Borna Disease Virus Nucleoprotein

Identification of the Immunodominant H-2Kk-Restricted Cytotoxic T-Cell Epitope in the Borna Disease Virus Nucleoprotein

We mapped the CTL epitope in BDV p40 by two comple- mentary experimental approaches. In a first approach, we gen- erated C-terminally truncated versions of p40 that were sub- sequently introduced into recombinant vaccinia viruses in order to express them in L929 cells. These cells were then used as target cells in cytotoxicity assays with lymphocytes from brains of BDV-infected mice with acute neurological disease. In a second approach, we screened the amino acid sequence of p40 for motifs that conform to the known consensus sequence for H-2k-restricted T-cell epitopes. Chemically synthesized peptides corresponding to candidate p40 epitopes were then added to the culture medium of L929 target cells to achieve their loading onto surface MHC class I complexes. An unex- pected difficulty of the first approach was that vaccinia viruses carrying p40 variants that lacked 206 or more C-terminal amino acid residues could not be rescued. A second difficulty was that those C-terminally truncated p40 versions that could be rescued did not accumulate to high levels in infected cells, although the corresponding mRNAs were abundantly present. Since L929 cells infected with these recombinant vaccinia vi- ruses were excellent targets for BDV-specific CTLs, it appears that the observed decreased stability of the mutants actually promoted efficient surface presentation of p40-derived pep- tides. Similar observations were reported with C-terminal trun- cation mutant forms of the nucleoprotein of influenza virus A/NT/60/68 (H3N2) (48) and the large T antigen of simian FIG. 3. N- and C-terminally elongated versions of TELEISSI are
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Arthritogenic T cell epitope in glucose 6 phosphate isomerase induced arthritis

Arthritogenic T cell epitope in glucose 6 phosphate isomerase induced arthritis

bovine (type II collagen) CII 256–270 (GEPGIAGFKGEQGPK), the dominant epitope of collagen-induced arthritis (CIA), at the major histocompatibility complex (MHC) binding sites [4]. Of note is that arthritis similar to GPI-induced arthritis was gener- ated by immunisation with a short 15-mer single peptide in genetically unaltered mice. By analysis of peptide-induced arthritis, we found that hGPI 325–339 -primed Th17 cells reacted

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Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor cells.

Fine structure of a virus-encoded helper T-cell epitope expressed on FBL-3 tumor cells.

To understand peptide-major histocompatibility complex MHC interactions and the subsequent recognition of peptides by specific T cells, we used peptides of decreasing lengths to determin[r]

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Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein.

Definition of a minimal optimal cytotoxic T-cell epitope within the hepatitis B virus nucleocapsid protein.

The aim of the present study was to identify the minimal optimal sequence recognized by HBcAg1ll27-specific CTLs in order to more thoroughly characterize the CTL response to this epitope[r]

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Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope.

Protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric T-cell epitope.

Spleen cells from mice primed with the recombinant vaccinia virus MCMV-ieI-VAC, encoding pp89 left panel, or with the recombinant AS-mer, encoding a deletion mutant of pp89 that lacks th[r]

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Presentation of an immunodominant T-cell epitope of hepatitis B surface antigen by the HLA-DPw4 molecule.

Presentation of an immunodominant T-cell epitope of hepatitis B surface antigen by the HLA-DPw4 molecule.

Antibody DA6.231, with broad specificity for DR and DP, and antibody B7/21, specific for DP antigens, were tested for their capacity to inhibit the proliferative response of the HBsAg-sp[r]

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Three dimensional structure directs T-cell epitope dominance associated with allergy

Three dimensional structure directs T-cell epitope dominance associated with allergy

The dependence of CD4+ epitope immunogenicity on local structural context has been examined for a number of epitopes and antigens. Epitope presentation often may depend on an initial proteolytic-processing event. The engineering of a nearby dibasic protease-recognition sequence dramatically increased the presentation of an epitope in hen egg lysozyme [12]. The blocking of a cleav- age site substantially reduced the overall immunogenicity of tetanus toxoid, presumably because the cleavage was necessary to globally unlock protein unfolding and fur- ther processing [13]. A more general demonstration of the relationship between structure and epitope dominance relies on the correlation between protease-sensitivity and conformational flexibility. The relative probability that a particular protein segment will be cleaved by a protease can be estimated by structural parameters that indicate conformational flexibility, such as crystallographic B fac- tors, solvent-accessible surface area, or amide-group hydrogen/deuterium exchange (HX) [14-17]. Correla- tions of epitope dominance with one or more measures of flexibility has been reported for a number of antigens and allergens [18-22], but these studies have not identified the systematic exclusion of epitopes from the center of flexi- ble segments in allergens, as is expected if proteolysis pre- cedes MHCII binding.
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IN-SILICO T-CELL EPITOPE PREDICTION TOOL OF HEPATITIS C VIRUS (HCV)

IN-SILICO T-CELL EPITOPE PREDICTION TOOL OF HEPATITIS C VIRUS (HCV)

To get authentic and reliable model for prediction of the T-Cell epitopes of HCV, the protein sequence of hepatitis C virus (HCV) is retrieved from research papers (15-33) via pubMed-NCBI (www.ncbi.nlm.nih.gov /m/pubmed/) and database through which the tested epitopes were extracted. The length of the amino acids present in the T-cell epitopes of HCV differs ranging from six residues to above.

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Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope

Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope

We therefore analyzed whether TCR-redirected T cells dis- play a similar polyfunctional profile compared to SARS-spe- cific memory CD8 T cells. TCR-redirected T cells specific for NP44 (aa 216 to 225) were engineered from PBMC of three FIG. 3. Production of SARS-specific TCR-redirected T cells. (A) Isolation of NP44-specific T cell clone. NP44-specific CD8 ⫹ T cells were purified by FACS and cloned by limiting dilution assay. Clonal populations were expanded and subjected to two rounds of screening for CD107a ⫹ and/or IFN- ␥ ⫹ CD8 ⫹ T cells. (B) Determination of the TCR ␤ chain of the NP44-specific T cell clone by staining for the various TCR ␤ variable regions (TRBV). The percentages of the CD8 ⫹ T cells positive for the various TRBV are indicated. Further cloning of the TCR ␣ and ␤ chains of the T cell clone was carried out, and peripheral blood lymphocytes from a healthy donor were transduced with the SARS NP44 TCR retroviral vector. (C) Dot plot of V ␤ 4.3 expression in mock- or NP44-TCR transduced T cells from a representative healthy donor. The percentages of V ␤ 4.3 ⫹ T cells (CD8 ⫹ and CD8 ⫺ ) after gating on the CD3 ⫹ fraction of the PBMC are indicated in the upper and lower right quadrants. (D) Dot plot from representative SARS NP44-transduced T cells incubated with target cells loaded with NP44 peptide. The percentages of IFN- ␥ ⫹ or CD107a ⫹ T cells (CD8 ⫹ and CD8 ⫺ ) after gating on the CD3 ⫹ fraction of the PBMC are indicated in the upper and lower right quadrants. (E) For functional avidity, NP44-specific T cell clone or SARS NP44 TCR-transduced T cells were incubated with target cells pulsed with the indicated concentrations of NP44 peptide. The percent maximum IFN- ␥ ⫹ response was plotted against the concentrations of NP44 peptide, whereby the maximum IFN- ␥ ⫹ response at 1 ␮ g/ml was set as 100%. The data shown are the mean values of three experiments with standard error bars as indicated. (F) For recognition of the endogenous SARS antigen, the SARS NP44-specific T cell clone and NP44 TCR-transduced T cells were incubated with target cells infected with a vaccinia virus construct expressing the SARS spike (S) (negative control) or nucleocapsid (NP) protein at an MOI of 5 and stained for CD107a. The percentages of CD107a ⫹ cells in the total CD8 ⫹ population are shown.
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