Search results for "major histocompatibility complex"
showing 10 items of 263 documents
Exogenous introduction of an immunodominant peptide from the non-structural IE1 protein of human cytomegalovirus into the MHC class I presentation pa…
2008
Exogenous introduction of particle-associated proteins of human cytomegalovirus (HCMV) into the major histocompatibility complex (MHC) class I presentation pathway by subviral dense bodies (DB) is an effective way to sensitize cells against CD8 T-cell (CTL) recognition and killing. Consequently, these particles have been proposed as a platform for vaccine development. We have developed a strategy to refine the antigenic composition of DB. For proof of principle, an HCMV recombinant (RV-VM3) was generated that encoded the immunodominant CTL determinant IE1TMY from the IE1 protein in fusion with the major constituent of DB, the tegument protein pp65. To generate RV-VM3, a bacterial artificial…
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…
Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth.
2013
International audience; Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex cl…
Development of T cell clones reactive to two defined restriction elements in conjunction with two defined epitopes of antigen
1985
A previously described pig insulin (PI)-specific T cell line of (B10 X B10.BR)F1 origin was assayed for its reactivity with species variants of insulin in the presence of antigen-presenting cells (APC) of various H-2 haplotypes. In addition to its reactivity with PI and bovine insulin (BI) in the context of syngeneic F1 (H-2b X k)-APC, a weak cross-reactivity was observed with parental B10 (H-2b)-APC and BI but not PI. The cross-reactive cells could be selected out by several restimulations with the combination of BI and B10-APC. From the resulting, strongly cross-reactive T cell line several interleukin 2-dependent sublines were developed which did not require antigen-specific restimulatio…
BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
2020
BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial1. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 µg dose levels. BNT162b2 elicited strong antibody …
Mapping and expression pattern analysis of key components of the major histocompatibility complex class I antigen processing and presentation pathway…
2001
Renal cell carcinoma (RCC) represent approximately 5% of all cancer deaths. At the time of presentation, over 50% of the patients have already developed locally advanced or metastatic disease with five-year survival rates of less than 20%. Although relative resistant to conventional regimens, RCC are partially susceptible to T cell-based immunotherapy. To further develop this treatment modality, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied for both the mapping of the key components of the major histocompatibility complex (MHC) class I antigen processing and presentation machinery (APM) and the characterization of the constitutive and cytokine-regulated protein e…
Mycoplasma fermentans-derived lipid inhibits class II major histocompatibility complex expression without mediation by interleukin-6, interleukin-10,…
1996
Mycoplasma cause several diseases in man and animals. Some strains can chronically infect humans, leading to fever or inflammatory syndromes such as arthritis, particularly in immunosuppressed patients. A set of pathogenicity factors shared by many mollicutes may be membrane components that activate macrophages to secrete cytokines and other inflammatory mediators. Mycoplasma-derived high molecular weight material (MDHM) is a macrophage-activating amphiphilic lipid which was purified from Mycoplasma fermentans. We studied the influence of MDHM on the expression of major histocompatibility complex (MHC) class II molecules by mouse resident peritoneal macrophages with an ELISA. Highly purifie…
Tumor associated antigens in human renal cell carcinoma: MHC restricted recognition by cytotoxic T lymphocytes.
1996
Based on previous studies in human melanoma leading to the molecular cloning of genes encoding peptide antigens recognized by MHC-restricted cytotoxic T lymphocytes (CTL) we extended our efforts to renal cancer systems established in tissue culture. In two patients we obtained stable CD8+ CTL clones with high cytolytic activity for the corresponding autologous tumor cell line in vitro. Neither autologous EBV-transformed B lymphocytes or PHA-activated PBL nor natural killer targets K562 were lysed by these CTL clones. MZ1257-RCC CTL5-30 lysed autologous tumor cells as well as normal kidney cell cultures in an HLA-A2 restricted fashion. Further specificity analysis showed cross reactivity wit…
Tonic T cell signalling and T cell tolerance as opposite effects of self-recognition on dendritic cells.
2010
Naive T cells spend most of their time scanning the surface of dendritic cells (DCs), indicating that self-MHC/T cell receptor (TCR) interactions between these immune cells occur routinely in peripheral organs during the steady state. Peripheral self-MHC recognition on DCs drives seemingly opposing effects in the absence of inflammatory stimuli such as deletion of certain self-reactive T cells as well as maintenance of the T cell responsiveness to antigen, both of which shape the T cell repertoire and regulate T cell responses. Here we review recent data on the role of self-MHC recognition on steady-state DCs in the periphery and propose that interactions between T cells and steady-state DC…
The Role of the Major Histocompatibility Gene Complex in Murine Cytotoxic T Cell Responses
1980
Publisher Summary An interpretation of the function of major histocompatibility complex (MHC) in cytotoxic T cell responses requires making certain assumptions, which, because of the lack of experimental data, are often based on intuition. This chapter discusses some specific aspects of the role of MHC in cytotoxic T cell responses. It also summarizes the expression of T cell-mediated responses to alloantigens. It also focuses on H-2-restricted cytotoxic T lymphocytes (CTL) responses and discusses the influence of the MHC on cytotoxic T cell specificity and CTL responsiveness against foreign antigens. T cell responses to alloantigens mirror all the functional activities seen in H-2-restrict…