Search results for "Antigen processing"
showing 10 items of 71 documents
Minimal Information About an Immuno-Peptidomics Experiment (MIAIPE)
2018
Minimal Information about an Immuno-Peptidomics Experiment (MIAIPE) is an initiative of the members of the Human Immuno-Peptidome Project (HIPP), an international program organized by the Human Proteome Organization (HUPO). The aim of the MIAIPE guidelines is to deliver technical guidelines representing the minimal information required to sufficiently support the evaluation and interpretation of immunopeptidomics experiments. The MIAIPE document has been designed to report essential information about sample preparation, mass spectrometric measurement and associated mass spectrometry (MS)-related bioinformatics aspects that are unique to immunopeptidomics and may not be covered by the genera…
HER-2/neu-mediated regulation of components of the MHC class I antigen-processing pathway.
2004
Abstract Because of its amplification and/or overexpression in many human tumors, the HER-2/neu proto-oncogene represents an attractive target for T-cell-mediated vaccination strategies. However, overexpression of oncogenes is often associated with defective expression of components of the MHC class I antigen-processing machinery (APM), thereby resulting in an immune escape phenotype of oncogene-transformed cells. To determine whether HER-2/neu influences the MHC class I antigen-processing pathway, the expression pattern of different APM components was examined in murine in vitro models of constitutive and tetracycline-controlled HER-2/neu expression. In comparison with HER-2/neu− control c…
An MHC class II-expressing T cell clone presenting conventional antigen lacks the ability to present bacterial superantigen.
1995
We have analyzed the response of rat T cells to myelin basic protein (MBP) and the bacterial superantigen, staphylococcal enterotoxin E (SEE). Rat T cells reactive with MBP can respond to SEE presented by spleen cells but not to SEE presented by LOA, a rat T cell clone that expresses both I-A and I-E MHC class II molecules, even though LOA is much more efficient than splenic APC in the presentation of MBP. The inability of LOA to present superantigen is not due to a structural difference in MHC II molecules between LOA and the splenic APC or to differential expression of major accessory/adhesion molecules, including CD2, CD5, CD4 and CD44, on LOA. The non-responsiveness of SEE/LOA-induced T…
HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification
2014
Summary The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8+ T cell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ∼30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ∼60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a giv…
Cloning and functional analyses of the mouse tapasin promoter
2003
The expression of tapasin is critical for an optimized MHC class I assembly and stable MHC class I surface expression. Thus, impaired MHC class I antigen expression of tumors can be attributable to tapasin downregulation. In order to understand the molecular mechanisms of deficient tapasin expression, the mouse tapasin promoter region and its 5'-flanking sequences were characterized. The mouse tapasin promoter lacks the TATA box and its transcription is initiated at multiple sites within a 51-nucleotide stretch. Sequence analyses revealed transcription factor binding motifs for NF-kappaB, GATA, E2F, p300, AP1, SP1 and IRF-1/2. Detailed analysis of deletion mutants and elimination of transcr…
Heat shock protein-peptide complexes for use in vaccines
1996
Abstract The heat shock proteins gp96, HSP70, and HSP90 are complexed to a diverse array of cellular proteins and peptides as a consequence of their chaperone functions. There is good experimental evidence that vaccination with these heat shock protein-peptide complexes elicit immune responses against chaperoned peptide antigens. As shown with gp96, this requires internalization of the heat shock protein-peptide complexes by macrophages and processing of the chaperoned peptides for class I restricted presentation. Via this process, primarily CD8+ antigen-specific T cells are primed by gp96 vaccination. This might represent a general mechanism for priming of MHC-class I restricted T cells by…
The Efficacy of Antigen Processing Is Critical for Protection against Cytomegalovirus Disease in the Presence of Viral Immune Evasion Proteins▿
2009
ABSTRACT Cytomegaloviruses (CMVs) code for immunoevasins, glycoproteins that are specifically dedicated to interfere with the presentation of antigenic peptides to CD8 T cells. Nonetheless, the biological outcome is not an immune evasion of the virus, since CD8 T cells can control CMV infection even when immunoevasins are expressed. Here, we compare the processing of a protective and a nonprotective epitope derived from the same viral protein, the antiapoptotic protein M45 in the murine model. The data provide evidence to conclude that protection against CMVs critically depends on antigenic peptides generated in an amount sufficient to exhaust the inhibitory capacity of immunoevasins.
Down-regulation of the MHC class I antigen-processing machinery after oncogenic transformation of murine fibroblasts
1998
Malignant transformation is often associated with genetic alterations providing tumor cells with mechanisms for escape from immune surveillance. Human and murine tumors of various origin as well as in vitro models of viral and oncogenic transformation express reduced levels of major histocompatibility complex (MHC) class I antigens resulting in decreased sensitivity to MHC class I-restricted cytotoxic T lymphocyte (CTL)-mediated lysis. We here investigate whether the suppressed MHC class I surface expression of ras-transformed fibroblasts is due to dysregulation of the genes of the antigen-processing machinery, the peptide transporters TAP-1 and TAP-2 and the proteasome subunits LMP-2 and L…
Coordinate downregulation of multiple MHC class I antigen processing genes in chemical-induced murine tumor cell lines of distinct origin
2000
In murine tumor cell lines, downregulation of MHC class I surface expression has been frequently detected, but the underlying molecular mechanisms of such deficiencies have not been defined. In this study, murine tumor cell lines of different histology derived from spontaneous or from chemical-induced tumors were analyzed for the expression of multiple components of the major histocompatibility complex (MHC) class I antigen-processing machinery (APM), including the peptide transporter TAP, the interferon (IFN)-gamma inducible proteasome subunits and several chaperones. The tumor cell lines analyzed demonstrated a heterogeneous expression pattern of various APM components. In comparison to c…
RUNX3 and T-Bet in Immunopathogenesis of Ankylosing Spondylitis—Novel Targets for Therapy?
2019
Susceptibility to ankylosing spondylitis (AS) is polygenic with more than 100 genes identified to date. These include HLA-B27 and the aminopeptidases (ERAP1, ERAP2, and LNPEPS), which are involved in antigen processing and presentation to T-cells, and several genes (IL23R, IL6R, STAT3, JAK2, IL1R1/2, IL12B, and IL7R) involved in IL23 driven pathways of inflammation. AS is also strongly associated with polymorphisms in two transcription factors, RUNX3 and T-bet (encoded by TBX21), which are important in T-cell development and function. The influence of these genes on the pathogenesis of AS and their potential for identifying drug targets is discussed here.