Search results for "Histocompatibility"
showing 10 items of 473 documents
CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated ant…
2003
Objective In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. Material and methods Flow-cy…
Rapid Detection of the ERV-K(C4) Retroviral Insertion Reveals Further Structural Polymorphism of the Complement C4 Genes in Old World Primates
2001
The fourth component of complement (C4) is coded for by two tandem-duplicated genes located in the class III region of the MHC of humans as well as a number of primates. A C4 gene size polymorphism giving rise to two gene variants of 16 and 22.3 kb length can be attributed to a complete endogenous retroviral insertion of 6.3 kb termed ERV-K(C4) in intron 9 of the long C4 genes. We developed a simple PCR-based screening assay to detect the presence of this insertion, and tested a number of unrelated animals from old world primate species. The presence of the ERV insertion in the orangutan, rhesus macaque and green monkey as well as its absence in gorillas and chimpanzees could be confirmed. …
Involvement of NO in contact hypersensitivity.
1998
The NO synthases (NOS) generate NO from L-arginine. High concentrations of NO have been shown to be responsible for tissue injury and cell death, while low concentrations of NO induce vasodilatation and other signaling effects. We have investigated the involvement of NO in contact hypersensitivity (CHS) reactions. CHS induced by treatment of BALB/c mice with the contact allergen 2,4-dinitrofluorobenzene (DNFB) was significantly reduced by the NOS inhibitor N-methyl-L-arginine (L-NMA), but not by the stereoisomer D-NMA, as shown by reduced ear swelling responses and evaluation of ear tissue sections. The CHS response was also reduced by aminoguanidine, which is known to preferentially inhibi…
µ-Calpain conversion of antiapoptotic Bfl-1 (BCL2A1) into a prodeath factor reveals two distinct alpha-helices inducing mitochondria-mediated apoptos…
2011
Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c r…
T cell-independent joint destruction
1998
Rheumatoid Arthritis (RA) is a chronic systemic disorder of unknown etiology. Although, early and late stages of the disease may be driven by different processes, affected joints are characterized by inflammation, synovial hyperplasia, and abnormal immune responses [1]. The abundance of T cells within the rheumatoid synovium as well as the association of certain major histocompatibility complex (MHC) class II molecules with RA [2] implied a central role for T cells in the pathophysiology of the disease. However, recent advances in molecular biology have fostered new concepts for the pathogenesis of RA. Specifically, the investigation of early stages of disease, the development of novel anim…
Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expre…
1998
The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post-implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)-gamma or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP-2 and LMP-7 and the peptide transporters TAP-1 and TAP-2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN-gamma regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human …
Bipartite regulation of different components of the MHC class I antigen-processing machinery during dendritic cell maturation
2001
Dendritic cells (DC) are professional antigen-presenting cells (APC) which proceed from immature to a mature stage during their final differentiation. Immature DC are highly effective in terms of antigen uptake and processing, whereas mature DC become potent immunostimulatory cells. Until now, the expression profiles of the major components of the MHC class I antigen-processing machinery (APM) during DC development have not been well characterized. In this study, the mRNA and protein expression levels of the IFN-gamma inducible proteasome subunits, of the proteasome activators PA28, and of key components required for peptide transport and MHC class I-peptide complex assembly have been evalu…
Functional deficiencies of components of the MHC class I antigen pathway in human tumors of epithelial origin
2000
An association between oncogenic transformation and repression of different components of the MHC class I antigen processing machinery (APM) have been described in murine model systems. In order to discover whether a similar correlation exists, human tumor cell lines of distinct histology with altered ras protein were analyzed for the expression of APM components utilizing RT-PCR and Western blot analyses. A heterogeneous expression pattern of MHC class I antigens, TAP peptide transporter, proteasome subunits, proteasome activator PA28 and the chaperones calnexin, calreticulin as well as tapasin was displayed by these tumor cell lines. Single or combined deficiencies in the expression and/o…
Characterizing the N-terminal processing motif of MHC class I ligands.
2008
Abstract Most peptide ligands presented by MHC class I molecules are the product of an intracellular pathway comprising protein breakdown in the cytosol, transport into the endoplasmic reticulum, and successive N-terminal trimming events. The efficiency of each of these processes depends on the amino acid sequence of the presented ligand and its precursors. Thus, relating the amino acid composition N-terminal of presented ligands to the sequence specificity of processes in the pathway gives insight into the usage of ligand precursors in vivo. Examining the amino acid composition upstream the true N terminus of MHC class I ligands, we demonstrate the existence of a distinct N-terminal proces…
Features of TAP-independent MHC class I ligands revealed by quantitative mass spectrometry.
2008
TAP is responsible for transferring cytosolic peptides into the ER, where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC class I surface expression and alters the presented peptide pattern. This key molecule in antigen processing is tackled by several viruses and lost in some tumors, rendering the altered cells less vulnerable to T cell-based immune surveillance. Using the TAP-deficient cell line LCL721.174 and its TAP-expressing progenitor cell line LCL721.45, we identified and quantified more than 160 HLA ligands, 50 of which were presented TAP-independently. Peptides which were predominantly presented on the TAP-deficient LCL721.174 cell line…