Search results for "PES"
showing 10 items of 5212 documents
Identification of HLA-A*0201-Restricted T Cell Epitopes Derived from the Novel Overexpressed Tumor Antigen Calcium-Activated Chloride Channel 2
2002
Abstract Vaccination against tumor Ags may become a promising treatment modality especially in cancer types where other therapeutic approaches fail. However, diversity of tumors requires that a multitude of Ags become available. Differential expression in normal vs cancerous tissues, both at the mRNA and the protein level, may identify Ag candidates. We have previously compared transcripts from squamous cell lung cancer and normal lung tissue using differential display analysis, and found a transcript that was overexpressed in malignant cells and was identical with the calcium-activated chloride channel 2 (CLCA2) gene. We have now selected HLA-A2-restricted peptides from CLCA2, and have gen…
Quantitation of antigen-reactive T cells in peripheral blood by IFNgamma-ELISPOT assay and chromium-release assay: a four-centre comparative trial
2000
The ELISPOT assay is increasingly being used for the monitoring of the induction of antigen-reactive T cells in cancer vaccination trials. In order to evaluate the reliability of T cell frequency analysis with the ELISPOT assay, a comparative study was performed in four European laboratories. Six samples from healthy subjects were analyzed for the frequency of influenza-reactive CD8+ T cells in peripheral blood mononuclear cells (PBMC) by IFNgamma-ELISPOT assay. In addition, one laboratory determined cytotoxic T cell precursor (CTL) frequencies in these samples by limiting dilution chromium-release assay (LDA), and three laboratories performed a variant of the LDA, the multiple microculture…
Identification of T cell epitopes by the use of rapidly generated mRNA fragments.
2004
Abstract Although the number of defined T cell epitopes of clinically relevant antigens is constantly increasing, there is still an enormous need to identify further peptides, processed from new antigens or presented by rare HLA molecules, respectively. Here we introduce a novel two-step approach for the rapid identification of T cell epitopes. It was established in the CMV infection model. From the peripheral blood of healthy donors sharing HLA-A1 according to HLA serotyping we isolated CD8 + T lymphocytes and generated dendritic cells (DCs). DCs were electroporated with CMV pp65 mRNA and tested for recognition by autologous CD8 + T lymphocytes in IFN-γ ELISPOT assays. In all 10 CMV-seropo…
TCR V alpha chain expression influences reactivity to the hapten TNP.
1997
We have recently demonstrated a remarkable selection of in vitro cultivated, TNP-specific polyclonal T cell lines for the expression of a TCR beta chain encoded by the V beta 8.2 gene. The goal of the present study was to analyse V alpha usage in V beta 8.2 T cells responsive to TNP, using TNP-specific T cell lines derived from three common strains of mice, as well as from V beta 8.2 transgenic mice. Results indicate that in vitro TNP stimulation of T cells from TNP-immune mice results in significant skewing of V alpha usage among responding V beta 8.2+ T cells, with overexpression observed for V alpha 3.2 and V alpha 8. These results indicate that V alpha expression influences recognition …
HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification
2014
Summary The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8+ T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ∼30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ∼60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a giv…
Tumors as elusive targets of T-cell-based active immunotherapy.
2003
The understanding of tumor-host interactions remains elusive despite significant progress in the identification of tumor antigens (TAs) recognized by autologous T cells. In particular, most human tumors do not regress and continue to grow in spite of spontaneous or immunization-induced immune responses demonstrated in circulating lymphocytes. Indeed, systemic immune responses might insufficiently address the complexity of tumor-host interactions because of factors, such as (1) the lack of productive T-cell receptor (TCR) engagement with epitope owing to qualitative and/or quantitative defects in the generation and maintenance of the immune response, (2) insufficient costimulation provided b…
Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles.
2005
Induction of high frequencies of specific T cells by vaccination requires prime-boost regimens. To reach optimal immune responses, it is necessary to use different vectors for priming and boosting as e.g. DNA vaccination followed by boosting with a recombinant viral vector. Here, we show that vaccines based on virus-like particles (VLP) displaying peptide epitopes are equally effective to induce CTL responses if used in a homologous or heterologous prime-boost setting. Strikingly, high frequencies (>20% of CD8(+) cells) of protective CTL could be induced and maintained by weekly injection of VLP. Thus, the use of VLP may avoid the requirement for complicated heterologous prime-boost regi…
The use of clonal mRNA as an antigenic format for the detection of antigen-specific T lymphocytes in IFN-gamma ELISPOT assays.
2003
Abstract Most assay systems for the quantification of antigen-specific T-cell responses in infectious, malignant and autoimmune disease depend on the peptide antigen format and are therefore restricted to known epitopes and their presenting HLA molecules. Here we tested in ELISPOT assays the application of in vitro-transcribed clonal mRNA as an alternative antigen format covering all potential epitopes of a given antigen. As model antigens, we chose pp65 of human cytomegalovirus (HCMV) and human tyrosinase (hTyr). Antigen-presenting cells (APC) were K562 cells stably transfected with single HLA class I alleles and autologous dendritic cells (DC). As effectors, we applied in vitro-generated …
In vitro T-cell immunogenicity of oligopeptides derived from the region 92-110 of the 16-kDa protein ofMycobacterium tuberculosis
2004
The 16-kDa protein of Mycobacterium tuberculosis provokes specific immune responses; it is thus a target for the development of peptide-based diagnostic reagents and subunit vaccines. Previous studies have demonstrated the presence of several regions containing murine and human T-cell epitopes. Within the 91–110 immunodominant domain, we found that peptides comprising the sequence of 91SEFAYGSFVRTVSL104 elicit specific T-cell responses in both human T-cell clones and human peripheral blood mononuclear cells (PBMC) from PPD+ (purified protein derivative) individuals. Elongation of this peptide towards the C-terminal end did not provide more effective peptides, but the removal of residue 91Se…
Shared determinants between virus-infected and trinitrophenyl-conjugated H-2-identical target cells detected in cell-mediated lympholysis
1976
Infection of H-2-identical mice with either lymphocytic choriomeningitis (LCM) virus, vaccinia virus, or paramyxo (Sendai) virus resulted in the generation of specifically sensitized cytotoxic T lymphocytes (CTL). CTL generated in vitro against 2,4,6-trinitrophenyl (TNP)-conjugated syngeneic stimulator cells were specifically cytotoxic for TNP-conjugated H-2K (D) region identical targets. Both LCM and vaccinia-induced CTL, however, were found to be strongly cytotoxic towards TNP-conjugated, H-2K(D) region-identical target cells. In contrast, Sendai virus-induced CTL did not lyse TNP-conjugated, syngeneic target cells. Inhibition experiments using cold targets suggested that shared antigenic…