Search results for "major histocompatibility complex"
showing 10 items of 263 documents
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…
Mutant MHC class II epitopes drive therapeutic immune responses to cancer
2015
Tumour-specific mutations are ideal targets for cancer immunotherapy as they lack expression in healthy tissues and can potentially be recognized as neo-antigens by the mature T-cell repertoire. Their systematic targeting by vaccine approaches, however, has been hampered by the fact that every patient's tumour possesses a unique set of mutations ('the mutanome') that must first be identified. Recently, we proposed a personalized immunotherapy approach to target the full spectrum of a patient's individual tumour-specific mutations. Here we show in three independent murine tumour models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that, unexpectedly, the …
Human Papillomavirus Type 33 E7 Peptides Presented by HLA-DR*0402 to Tumor-Infiltrating T Cells in Cervical Cancer
2000
ABSTRACTSeveral characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins are constitutively expressed in HPV-positive cervical cancer and may serve as tumor rejection antigens. Five HPV types (16, 18, 31, 33, and 45) account for 80% of cervical cancer. Until now, the type of immune response capable of mediating an effective antitumor response has not been defined. In order to define the anticancer-directed immune response in situ, we characterized CD4+and CD8+sorted T cells from peripheral blood lymphocytes, freshly harvested tumor tissue, and tumor-infiltrating lymphocytes (TIL) from a p…
Optimized Protocol for the Detection of Multifunctional Epitope-Specific CD4+ T Cells Combining MHC-II Tetramer and Intracellular Cytokine Staining T…
2019
Analysis of multifunctional CD4+ T cells is fundamental for characterizing the immune responses to vaccination or infection. Major histocompatibility complex (MHC)/peptide tetramers represent a powerful technology for the detection of antigen-specific T cells by specific binding to their T-cell receptor, and their combination with functional assays is fundamental for characterizing the antigen-specific immune response. Here we optimized a protocol for the detection of multiple intracellular cytokines within epitope-specific CD4+ T cells identified by the MHC class II tetramer technology. The optimal procedure for assessing the functional activity of tetramer-binding CD4+ T cells was based o…
H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cyto…
2000
H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompati…
2002
To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal alphaDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c- cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When alphaDEC-205:OVA was injected subcutaneously, OVA protein was identified over a …
T-Cell Epitope Processing (The Epitope Flanking Regions Matter)
2009
Epitopes presented by major histocompatibility complex (MHC) class I molecules for cytotoxic T-lymphocyte (CTL) recognition are derived mainly from cytosolic proteins. Antigen presentation on the cell surface requires correct processing of epitopes by the proteasome, cytosolic and endoplasmic reticulum (ER) aminopeptidases, efficient TAP transport, and sufficient binding to MHC class I molecules. The efficiency of the epitope generation depends not only on the epitope itself but also on its flanking regions. To investigate preferences at the C-terminal epitope extension on processing and presentation, the SIINFEKL (S8L) epitope can be used as a model epitope. By exchanging the amino acids a…
Frequency-Analysis of Precursors of Cytotoxic T Lymphocytes in Radiation Chimeras: Enumeration of Antigenspecific CTL-P Restricted to Thymic MHC- and…
1984
The mechanisms controlling the acquisition of T cell restriction specificity and immunocompetence are, despite of numerous investigations, not well understood. From studies of the CTL-immune responsiveness in thymus- and bone marrow-grafted chimeric mice, it became apparent, that it is the thymus which is crucial not only for the maturation or T cells, but also for the specificity repertoire of the T cells (1,2). From these data it was suggested, that during intra-thymic maturation both mutational events and positive selection mechanisms influence the repertoire such that only T cells restricted to thymic epithelial cell MHC determinants mature and will be exported to the peripheral lymphoi…
HLA class I antigen abnormalities and immune escape by malignant cells
2002
Abbreviations used in this paper: APM, antigen processing machinery; β2m,β2 microglobulin; bp, base pair; CTL, cytotoxic T lymphocytes; ER, endoplasmic reticulum; HC, heavy chain; HNSCC, head and neck squamous cell carcinoma; IFN, interferon; IL, interleukin; KIR, killing inhibitory receptors; LMP, low molecular weight proteins; LOH, loss of heterozygosity; mAb, monoclonal antibody; MHC, major histocompatibility complex; NK, natural killer; PA, proteasome activator; PCR, polymerase chain reaction; RCC, renal cell carcinoma; SCLC, small cell-lung carcinoma; TAA, tumor-associated antigens; TAP, transporter associated with antigen processing; TCR, T cell receptor; TNF, tumor necrosis factor; w…
Induction of immunogenicity of a human renal-cell carcinoma cell line byTAP1-gene transfer
1999
Reduced expression of the major-histocompatibility-complex(MHC)-class-I antigens has been demonstrated in renal-cell carcinoma (RCC), and appeared to be associated with deficiencies in the expression and function of different components of the MHC-class-I-antigen-processing pathway and poor recognition by cytotoxic T-lymphocytes (CTL). In order to investigate the role of peptide transporters for the immunogenic phenotype of RCC, tumor cells were stably transfected with the human TAP1A gene. While the TAP1 transfectants showed heterogeneous TAP1-transgene expression pattern of mRNA and protein, high TAP1 expression and a TAP-controlled increase in MHC-class-I surface expression could be achi…