Search results for "MHC restriction"
showing 10 items of 41 documents
Current advances in γδ T cell-based tumor immunotherapy
2017
γδ T cells are a minor population (~5%) of CD3 T cells in the peripheral blood, but abound in other anatomic sites such as the intestine or the skin. There are two major subsets of γδ T cells: those that express Vd1 gene, paired with different Vγ elements, abound in the intestine and the skin, and recognize the major histocompatibility complex (MHC) class I-related molecules such as MHC class I-related molecule A, MHC class I-related molecule B, and UL16-binding protein expressed on many stressed and tumor cells. Conversely, γδ T cells expressing the Vδ2 gene paired with the Vγ9 chain are the predominant (50-90%) γδ T cell population in the peripheral blood and recognize phosphoant…
Targeting Acute Leukemia and Cancer by High-Affinity T-Cell-Receptor Transfer
2003
Accumulation and subsequent overexpression of human mdm2 (hdm2) and altered p53 protein is associated with high-level presentation of hdm2 and wild-type (wt) p53 derived peptides by major histocompatibility complex (MHC) class I molecules on a wide range of malignant cells. A major barrier to the design of broad-spectrum hdm2 and p53 specific immunotherapeutics for leukemia and cancer, however, has been the observation that low-level expression of hdm2 and wt p53 peptides by non-transformed tissues and cells results in self-tolerance of T-lymphocytes with high avidity for self-class I MHC / self-peptide complexes. Although the peripheral T-cell repertoire is mostly devoid of such high-avidi…
Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients
2007
Tetramers of MHC–peptide complexes are used for detection and characterization of antigen-specific T cell responses, but they require knowledge about both antigenic peptide and the MHC restriction element. The successful application of these reagents in human diseases involving CD4 + T cells is limited. Celiac disease, an intestinal inflammation driven by mucosal CD4 + T cells recognizing wheat gluten peptides in the context of disease-associated HLA-DQ molecules, is an ideal model to test the potential clinical use of these reagents. We investigated whether gluten-specific T cells can be detected in the peripheral blood of celiac disease patients using DQ2 tetramers. Nine DQ2 + patients a…
TAP off - tumors on
1997
Abstract The molecular characterization of T-cell-defined tumor-associated antigens has provided targets for cell-mediated immunotherapy for malignant diseases. The success of this strategy is negatively influenced by structural and functional abnormalities of major histocompatibility complex (MHC) class I molecules, which provide tumor cells with resistance to T-cell-mediated immune recognition. This article reviews the physiology of the MHC class I processing machinery and describes the deficiencies of this pathway in malignant cells.
The enemy in you: the interdependency of the localisation and antigenicity of proteins
2009
The subcellular localisation of protein components should be important for their antigenicity. This assumption is derived from the concept of MHC restriction, where CD4 and CD8 T lymphocytes can only interact with MHC II and MHC I surface receptors, respectively. If this mechanism applies, however, then intracellular components should have immunogenic effects mediated by MHC II and CD4 T lymphocytes as soon as they enter the extracellular space. Conversely, extracellular components should generate an immune response that is mediated by MHC I and CD8 lymphocytes when they breach the intracellular space and when they exceed a critical concentration. In this study, these hypotheses were invest…
Stimulation of human T cells by microbial 'superantigens'.
1991
The enterotoxins and the TSST of S. aureus, the erythrogenic toxins A and C of S. pyogenes and a still uncharacterized exoprotein of M. arthritidis belong to a family of exotoxins that have in common a potent mitogenic activity for T lymphocytes of several species. These proteins stimulate CD4+ and C8+ T cells, as well as a fraction of gamma delta TCR-bearing T cells by cross-linking variable parts of the T cell antigen receptor with MHC class II molecules on accessory or target cells. They are functionally bivalent molecules having distinct interaction sites for variable parts of the TCR and for nonpolymorphic parts of the MHC class II molecule. For alpha beta TCR-bearing T cells the V bet…
MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocyutes.
2003
The ability to activate CD4 T cells is restricted to antigen-presenting cells that express major histocompatibility complex (MHC) class II molecules. Parenchymal cells normally do not express MHC class II molecules; however, in clinical hepatitis, viral or autoimmune, hepatocytes often exhibit aberrant MHC class II expression. It is not known whether MHC class II-expressing hepatocytes can function as antigen-presenting cells, but it has been suggested that aberrant MHC class II expression by parenchymal cells may cause autoimmune disease. Therefore, we generated transgenic mice that specifically overexpress class II transactivator molecules in hepatocytes. Hepatocytes from these mice exhib…
Defective T helper response of hepatocyte-stimulated CD4 T cells impairs antiviral CD8 response and viral clearance.
2007
Background & Aims: In hepatitis, hepatocytes gain the ability to express major histocompatibility complex (MHC) class II molecules and to present antigen to CD4 T cells. Here, we investigated whether MHC class II-expressing hepatocytes influence in vitro the differentiation of CD4 T cells and in vivo the T-cell response to and control of viral infection. Methods: Class II transactivator-transgenic hepatocytes that constitutively express MHC class II molecules were used to stimulate CD4 T cells in vitro, and the effector response type of the stimulated CD4 T cells was determined. The in vivo relevance of the obtained findings was confirmed by infecting nontransgenic or class II transactivato…
Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals.
2007
Abstract Genetic modification of vaccines by linking the Ag to lysosomal or endosomal targeting signals has been used to route Ags into MHC class II processing compartments for improvement of CD4+ T cell responses. We report in this study that combining an N-terminal leader peptide with an MHC class I trafficking signal (MITD) attached to the C terminus of the Ag strongly improves the presentation of MHC class I and class II epitopes in human and murine dendritic cells (DCs). Such chimeric fusion proteins display a maturation state-dependent subcellular distribution pattern in immature and mature DCs, mimicking the dynamic trafficking properties of MHC molecules. T cell response analysis in…
Differential expression of alternative H2-M isoforms in B cells, dendritic cells and macrophages by proinflammatory cytokines.
1999
Major histocompatibility (MHC) class II heterodimers bind peptides generated by degradation of endocytosed antigens and display them on the surface of antigen presenting cells (APCs) for recognition by CD4+ T cells. Efficient loading of MHC class II molecules with peptides is catalyzed by the MHC class II-like molecule H2-M. The coordinate regulation of MHC class II and H2-M expression is a prerequisite for efficient MHC class II/peptide assembly in APCs determining both the generation of the T cell repertoire in the thymus and cellular immune responses in the periphery. Here we show that expression of H2-M and MHC class II genes is coordinately and cell type-specific regulated in splenic B…