Search results for "HLA-A"

B7/CD28 costimulation of T cells induces a distinct proteome pattern.

2005

Effective immune strategies for the eradication of human tumors require a detailed understanding of the interaction of tumor cells with the immune system, which might lead to an optimization of T cell responses. To understand the impact of B7-mediated costimulation on T cell activation comprehensive proteome analysis of B7-primed T cell populations were performed. Using this approach we identified different classes of proteins in T cells whose expression is either elevated or reduced upon B7-1- or B7-2-mediated CD28 costimulation. The altered proteins include regulators of the cell cycle and cell proliferation, signal transducers, components of the antigen processing machinery, transporters…

The Ability of Variant Peptides to Reverse the Nonresponsiveness of T Lymphocytes to the Wild-Type Sequence p53264–272 Epitope

2002

Abstract Recently, we observed that CTL specific for the wild-type (wt) sequence p53264–272 peptide could only be expanded ex vivo from PBMC of a subset of the HLA-A2.1+ normal donors or cancer patients tested. Surprisingly, the tumors of the responsive patients expressed normal levels of wt p53 and could be considered unlikely to present this epitope. In contrast, tumors of nonresponsive patients accumulated mutant p53 and were more likely to present this epitope. We sought to increase the responsive rate to the wt p53264–272 peptide of PBMC obtained from normal donors and patients by identifying more immunogenic variants of this peptide. Two such variants were generated by amino acid exch…

Human leucocyte antigen-A2 restricted and Mycobacterium tuberculosis 19-kDa antigen-specific CD8+ T-cell responses are oligoclonal and exhibit a T-ce…

2001

CD8+ T cells can be grouped into two different types of secretory T lymphocytes, based on the cytokine-secretion pattern upon antigen exposure: those with a T-cell cytotoxic type 1 response (Tc1), which secrete interferon-gamma (IFN-gamma), or those with a T-cell cytotoxic type 2 response, which secrete interleukin (IL)-4 and IL-10. We examined the CD8+ T-cell response directed against an immunodominant human leucocyte antigen (HLA)-A2-presented peptide derived from a 19-kDa Mycobacterium tuberculosis-associated antigen. T cells were examined by functional analysis and by T-cell receptor (TCR) complementarity-determining region 3 (CDR3)-spectratyping, which defines the complexity of a T-cel…

Oral immunization with HCV-NS3-transformed Salmonella: induction of HCV-specific CTL in a transgenic mouse model.

2001

Abstract Background & Aims: The ability to induce cytotoxic T cells is considered an important feature of a candidate hepatitis C virus (HCV) vaccine. We used an oral immunization strategy with attenuated HCV-NS3–transformed Salmonella typhimurium to deliver DNA directly to the gut-associated lymphoid tissue. Methods: HLA-A2.1 transgenic mice were immunized once with transformed attenuated Salmonella . HCV-specific CD8 + T cells were analyzed in vitro as well as in vivo by challenge of mice with recombinant HCV-NS3 vaccinia virus. Results: Salmonella (10 8 colony-forming units; 20 μg plasmid DNA) induced cytotoxic and IFN-γ–producing CD8 + T cells specific for the immunodominant epitope NS3…

Wharton's jelly mesenchymal stem cells immunomodulatory molecules: their journey from umbilical cord to differentieted cells.

2014

Transporter (TAP)- and proteasome-independent presentation of a melanoma-associated tyrosinase epitope.

2000

The melanosomal protein tyrosinase is considered as a target of specific immunotherapy against melanoma. Two tyrosinase-derived peptides are presented in association with HLA-A2.1 [Wolfel et al., Eur. J. Immunol., 24, 759-764 (1994)]. Peptide 1-9 (MLLAVLYCL) is generated from the putative signal sequence. The internal peptide 369-377 is posttranslationally converted at residue 371, and its presentation is dependent on functional TAP transporters and proteasomes [Mosse et al., J. exp. Med.187, 37-48 (1998)]. Herein, we report on the processing and transport requirements for the signal sequence-derived peptide 1-9 that were studied in parallel to those for peptide 369-377. After infection of …

Parvovirus H-1-Induced Tumor Cell Death Enhances Human Immune Response In Vitro via Increased Phagocytosis, Maturation, and Cross-Presentation by Den…

2005

Oncotropic and oncolytic viruses have attracted high attention as antitumor agents because they preferentially kill cancer cells in vitro and reduce the incidence of spontaneous, induced, or implanted animal tumors. Some autonomous parvoviruses (H-1, minute virus of mice) and derived recombinant vectors are currently under preclinical evaluation. Still not fully understood, their antitumor properties involve more than just tumor cell killing. Because wild-type parvovirus-mediated tumor cell lysates (TCLs) may trigger antigen-presenting cells (APCs) to augment the host immune repertoire, we analyzed phagocytosis, maturation, and crosspresentation of H-1-induced TCLs by human dendritic cells …

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…