Search results for "MHC"

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…

Major Histocompatibility Complex Modulation and Loss

2002

Relationship between HLA I surface expression and different cytopathic effects produced after herpes simplex virus infection in vitro.

1992

In the present study, we investigated the effects of herpes simplex virus (HSV) infection on the expression of HLA class I antigens and beta 2-microglobulin in human fibroblasts. The mRNA abundance for HLA class I was shown to be strongly reduced after infection with HSV strains either producing cell rounding or fusion from within (FFWI), however, HLA class I expression on the surface of cells is strongly reduced only after appearance of FFWI. Using a ts mutant (ts 78R) or CyA in combination with a fusion from without (FFWO) inducing strain of HSV, this loss of HLA class I antigens is assumed to be correlated to the rearrangement of the cell membrane during the fusion process itself as a la…

Imatinib Mesylate and Nilotinib Affect the MHC-Class I Presentation by Modulating the Proteasomal Processing of Antigenic Peptides.

2009

Abstract Abstract 2169 Poster Board II-146 The tyrosine kinase inhibitors (TKIs) Imatinib mesylate (IM, Gleevec, Glivec) and nilotinib (Tasigna, AMN) are currently used in treatment of chronic myeloid leukaemia (CML). IM has been described to influence the function and differentiation of antigen presenting cells, to inhibit the effector function of T lymphocytes and to decrease the immunogenicity of CML cells by downregulation of tumor associated antigens. In the present study, we analyzed the effect of IM and AMN on proteasomal activity in IM-sensitive or IM/AMN- resistant CML cells as well as in patient samples using a biotinylated active site-directed probe, which, covalently binds and l…

EFFECT OF M-LOCUS DEPENDENT T-CELL PROLIFERATION UPON THE INDUCTION OF ANTI H-2 CYTOTOXIC T EFFECTOR CELLS

1975

SUMMARY The influence of M-locus dependent T cell proliferation on the induction of anti H-2 cytotoxic T lymphocytes (CTL) was tested in an in vitro murine cytotoxic allograft model. BALB/c (or CBA/H) derived responder cells (H-2d or H-2k) were cultured together with either C57BL derived fibroblasts or C57BL derived (H-2b), U.V. light irradiated, splenic lymphocytes. These stimulator cells lack functionally active lymphocyte activating determinants (LADs), but display serologically defined (SD) H-2 antigenic specificities. The cytotoxic anti SD-activity obtained was weak. Under certain experimental conditions, the addition of stimulator cells which are H-2 identical to the responder cells b…

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…

THU0231 IL-17 polarization of mait cells derive from the activation of two different pathways

2017

Background Primary Sjogren Syndrome (pSS) is a chronic inflammatory disorder affecting exocrine glands. Both IL-23 and the downstream cytokines IL-17 and IL-22 are recognised as key players in the disease. Therefore, the identification of the cellular sources and inducers of IL-17 is crucial in the understanding of the drivers of inflammation in pSS. Mucosal-associated invariant T (MAIT) cells recognize riboflavin derivatives presented by the MHC class I-like molecule MR1. Objectives Recently, MAIT cells have been implicated in the pathogenesis of autoimmune disorders and found expanded in salivary glands of pSS patients. Their expression of IL7R and IL23R, makes them potential contributors…

Improved detection of melanoma antigen-specific T cells expressing low or high levels of CD8 by HLA-A2 tetramers presenting a Melan-A/Mart-1 peptide …

2001

MHC class I tetramers containing peptide epitopes are sensitive tools for detecting antigen-specific CD8(+) T-cell responses. We demonstrate here that binding of HLA-A2 tetramers to CD8(+) T cells specific for the melanoma-associated antigen Melan-A/MART-1 can be fine-tuned by altering either the bound peptide epitope or residues in the alpha 3 domain of HLA-A2, which is important for CD8 binding. Antigen-specific T cells expressing high levels of CD8 could be detected using HLA-A2 tetramers containing the peptide AAGIGILTV, an epitope which is naturally processed and presented from Melan-A/MART-1. In contrast, low CD8-expressing, antigen-specific T cells could be detected efficiently only …

Response to Comment on “Characterizing the N-Terminal Processing Motif of MHC Class I Ligands”

2008

The possibility that ERAAP plays a role in limiting the presentation of peptides derived from signal peptides may be tempting from an immunologist’s view. In eukaryotic cells, signal peptides have a mean length of 22 amino acids and are removed by signal peptide peptidases from the N terminus of

Analysis of Invariant Chain Processing in 3 Day Cultured Rat Langerhans Cells

1995

MHC class II molecules, critical peptide binding elements involved in the presentation of exogenous antigen to T helper cells, are expressed constitutively by Langerhans cells (LC) within their epidermal microenvironment. Several studies in mouse and man demonstrated, that short term in vitro culture of LC entails remarkable functional and penotypic alterations, including a profound increase of class II elements exposed at the LC’s surface1. Biosynthetic analysis revealed a downregulation of class II synthesis during the culture period2,3. In recent work on rat LC we described the uncoupling of the coordinately regulated biosynthesis of class II and invariant chain proteins in the course of…