Search results for "epitope"
showing 10 items of 455 documents
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…
Towards the Development of Antitumor Vaccines: A Synthetic Conjugate of a Tumor-Associated MUC1 Glycopeptide Antigen and a Tetanus Toxin Epitope.
2000
Proliferation of cytotoxic T-cells, a prerequisite for the development of antitumor vaccines, was induced by 1, but not by its partial structures A and B. The conjugate 1 containing a tumor-associated Sialyl-TN -MUC-1 glycopeptide antigen A and a T-cell epitope B of tetanus toxin was synthesized by fragment condensation on a solid phase.
Synthesis of tumor-associated glycopeptide antigens for the development of tumor-selective vaccines
2004
In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete formation of the glycan side-chains resulting from a premature sialylation, additional peptide epitopes become accessible to the immune system in mucin-type glycoproteins on tumor cells. These tumor-associated structure alterations constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens, glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor-associated sialyl-T(N), alpha2,6-sialyl-T and alpha2,3-sialyl-T antigens have been synthesized. Employing different linkers such as the…
Biomimetic synthesis of the tumor-associated (2,3)-sialyl-T antigen and its incorporation into glycopeptide antigens from the mucins MUC1 and MUC4.
2004
Glycoproteins on epithelial tumor cells often exhibit aberrant glycosylation profiles. The incomplete formation of the glycan side chains resulting from a down-regulated glucosamine transfer and a premature sialylation results in additional peptide epitopes, which become accessible to the immune system in mucin-type glycoproteins. These cancer-specific structure alterations are considered to be a promising basis for selective immunological attack on tumor cells. Among the tumor-associated saccharide antigens, the (2,3)-sialyl-T antigen has been identified as the most abundant glycan, found in several different carcinoma cell lines. According to a linear biomimetic strategy, the (2,3)-sialyl…
Dendritic cell aggresome-like-induced structure formation and delayed antigen presentation coincide in influenza virus-infected dendritic cells.
2005
Abstract Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC cl…
Transcutaneous immunization with imiquimod is amplified by CD40 ligation and results in sustained cytotoxic T-lymphocyte activation and tumor protect…
1999
Transcutaneous immunization (TCI) using ligands of Toll-like receptors (TLRs) and cytotoxic T-lymphocyte (CTL) epitopes lead to the induction of potent T-cell responses. To characterize the efficacy of TCI-mediated CTL activation, we monitored the frequency and functional activity of specific CTL induced with TCI using the ovalbumin-derived epitope SIINFEKL composed in creme containing the synthetic TLR7 ligand R-837. We found that the frequency and activity decayed rapidly 10 d post-TCI. Consistently, no significant memory T-cell formation was detectable. In a prophylactic vaccination setting, TCI was protective against a lethal challenge with ovalbumin expressing EG.7 thymoma cells when t…