Search results for "MHC"
showing 10 items of 233 documents
Immune Response to Tumor Stress Proteins—Implications for Vaccine Development Against Cancer
2000
Publisher Summary Stress proteins or heat shock proteins (HSP) belong to the most conserved proteins. The conservation of stress proteins stems from their basic and vital role in cells: Prevention of protein aggregation under stress and physiological conditions. Stress proteins are important target antigens in autoimmune diseases and during certain bacterial infections. This chapter reviews the immunogenicity of stress proteins of tumor cells, stimulation of T cell response by tumor stress proteins and implications this Tcell response have for immunity against the tumor or autoimmunity. The expression of stress proteins in cancer is altered. An overexpression of constitutively expressed or …
The T-cell response in patients with cancer
2002
Publisher Summary The chapter examines several methods to measure human T-cell responses, including ELISPOT analysis, intracellular cytokine staining of immune cells after antigenic stimulation, limiting dilution analysis, conventional cloning, and molecular definition of the T-cell response either in the peripheral circulation or in situ in patients with cancer The chapter presents the cellular immune response in patients with cancer. The chapter explores the recent studies that suggest humoral immunity and T-cell-mediated immunity are closely linked. In addition, most of the data concerning antitumor immune responses have been generated using MHC class I tetramer reagents. The ultimate go…
Dendritic cells and the handling of antigen
2003
Dendritic cells (DC) are a sparsely distributed, migratory group of bone marrow-derived leucocytes that are specialized for the uptake, transport, processing and presentation of antigens to T cells [1,2]. At an immature stage of development DC are considered as the first-line sentinels in immune surveillance of peripheral tissues, including epithelia of the skin and mucosal surfaces, where they sample continuously the antigenic local microenvironment by uptake of self- and exogenous antigen via macropinocytosis/endocytosis [3,4]. The efficiency of DC to initiate an immune response against infectious disease is due to their constant trafficking between peripheral tissues and draining lymph n…
Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells
2011
Abstract Human mature dendritic cells (DCs) can efficiently stimulate natural killer (NK)–cell responses without being targeted by their cytotoxicity. To understand this important regulatory crosstalk, we characterized the development of the immunologic synapse between mature DCs and resting NK cells. Conjugates between these 2 innate leukocyte populations formed rapidly, persisted for prolonged time periods and matured with DC-derived f-actin polymerization at the synapse. Polarization of IL-12 and IL-12R to the synapse coincided with f-actin polymerization, while other activating and inhibitory molecules were enriched at the interface between DCs and NK cells earlier. Functional assays re…
Costimulatory signalling potential of murine MHC class II‐positive T‐clone cells
1996
Activated human and rat T cells as well as mouse T-cell clones have been reported to synthesize and express major histocompatibility complex (MHC) class II molecules. However, the capacity of class II+ antigen (Ag) presenting T cells to induce proliferation of Ag-specific cloned T cells has been controversial. We analysed whether the failure of some T-cell clones to proliferate in response to Ag presented by class II+ T cells is because of a lack of costimulatory cytokine production by the antigen-presenting cells (APC). As a model system the mouse class II+ cloned BI/O4.1 T cells were used as APC in order to activate the T cell clone KIII5. This T-helper 1 (Th1) type, GAT (synthetic copoly…
Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus
2000
ABSTRACTThe mouse cytomegalovirus (MCMV)m152- andm06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide toH-2Ld-restricted CD8+cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of them152andm06genes in macr…
Synthesis and expression of MHC class II molecules in the absence of attached invariant chains by recombinant-interferon-gamma-activated bone-marrow-…
1987
Pure populations of in vitro propagated bone marrow-derived macrophages are constitutively Ia negative. Co-culturing of these cells with recombinant interferon-gamma (rIFN-gamma) resulted in the appearance of high amounts of Ia antigens at the cell surface of essentially all cells. The continuous presence of the stimulus was a prerequisite for sustained Ia expression because removal of the stimulus resulted in rapid decline of surface Ia. Two-dimensional (2D) gel analysis (1D isoelectric focusing, 2D sodium dodecyl sulfate-polyacrylamide gel electrophoresis) of class II molecules synthesized by rIFN-gamma-stimulated bone marrow macrophages (BMM phi) revealed that, in contrast to class II co…
Recognition of human renal cell carcinoma and melanoma by HLA-A2-restricted cytotoxic T lymphocytes is mediated by shared peptide epitopes and up-reg…
1996
Cytotoxic T lymphocytes (CTL) have previously been isolated from peripheral blood of patients with renal cell carcinoma (RCC). The CD8-positive CTL line MZ1257-CTL-5 (CTL-5) has been shown to lyse autologous cultured RCC cells in an HLA-A2 restricted fashion. Allogeneic, HLA-A2-matched RCC and melanoma cell lines were also lysed by CTL-5, suggesting that melanoma and renal cancer share antigenic determinants. The aim of the study was to determine whether RCC and melanoma share peptide epitopes that are recognized by CTL-5 in the context of HLA-A2 molecules. Peptides were acideulated from various cell lines, separated by reversed phase high performance liquid chromatography (RP-HPLC), and as…
Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis
2007
Challenged by scattered understanding of protective immunity to Mycobacterium tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted mycobacterial antigen Ag85B, a vaccine candidate that may be associated with immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10(-3) and 10(-7) M. After selection of the best matches, major histocompatibility complex class I/peptide tetramer complexes were constructed to measure the CD8+ T-cell responses directly ex vivo in peripheral blo…
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
2019
Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called a…