Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA encoding chicken interferon-gamma (chIFN-gamma) was cloned from a CD4+ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and expressed in Escherichia coli, COS- and CEC-32 fibroblast cell lines. In general, recombinant chicken IFN-gamma (rchIFN-gamma) expressed in the COS- and CEC-32 cell lines showed high bioactivity in vitro. The kinetics of IFN-gamma gene expression were examined in concanavalin A (Con A)-activated spleen lymphocytes by Northern blot and RT-PCR. IFN-gamma mRNA was detected as early as 30 min after Con A activation, reached peak expression at 2 h and then decreased starting at 4 h post Con A activation. A rabbit serum made to a synthetic peptide of IFN-gamma immunoprecipitated a 60 kDa E. coli maltose-binding fusion protein of recombinant IFN-gamma (MBP-IFN) and a 26-27 kDa secreted protein from COS cells and Con A-activated spleen cells. IFN-gamma inhibited vesicular stomatitis virus (VSV) mediated cytotoxicity of chicken embryonic fibroblast (CEF) cells and upregulated the expression of many macrophage cell surface antigens, including class I and class II major histocompatibility complex (MHC) proteins. These results show that chicken IFN-gamma possesses anti-viral activity and immunoregulates macrophage activities.
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PMID:Expression and functional characterization of recombinant chicken interferon-gamma. 943 75

The specificity of T cell-mediated immune responses is primarily determined by the interaction between the T cell receptor (TCR) and the antigenic peptide presented by the major histocompatibility complex (MHC) molecules. To refine our understanding of interactions between the TCR and the antigenic peptide of vesicular stomatitis virus (VSV) presented by the class I MHC molecule H-2Kb, we constructed a TCR alpha chain transgenic mouse in a TCR alpha-deficient background to define specific structural features in the TCR beta chain that are important for the recognition of the VSV/H-2Kb complex. We found that for a given peptide, a peptide-specific, highly conserved amino acid could always be identified at position 98 of the complementarity-determining region 3 (CDR3) loop of TCR beta chains. Further, we demonstrated that substitutions at position 6, but not position 1, of the VSV peptide induced compensatory changes in the TCR in both the amino acid residue at position 98 and the length of the CDR3beta loop. We conclude that the amino acid residue at position 98 of the CDR3beta loop is a key residue that plays a critical role in determining the specificity of TCR-VSV/H-2Kb interactions and that a specific length of the CDR3beta loop is required to facilitate such interactions. Further, these findings suggest that the alpha and beta chains of TCRs interact with amino acid residue(s) toward the N and C termini of the VSV peptide, respectively, providing functional evidence for the orientation of a TCR with its peptide/MHC ligand as observed in the crystal structures of TCR/peptide/MHC complexes.
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PMID:On defining the rules for interactions between the T cell receptor and its ligand: a critical role for a specific amino acid residue of the T cell receptor beta chain. 956 Feb 56

Pretreatment of chicken macrophages or fibroblasts with supernatants from concanavalin A-stimulated spleen cells or from the virus-transformed cell line reticuloendotheliovirus as source of interferon gamma (IFN-gamma) slows down subsequent sporozoite replication in the cells. To identify the presence of IFN-gamma, we combined four typical activities of IFN-gamma: inhibition of cytopathic effect of vesicular stomatitis virus on IFN-gamma-treated fibroblasts, cytostatic activity of IFN-gamma-activated macrophages, induction of major histocompatibility complex II antigen expression on IFN-gamma-activated fibroblasts and macrophages, and induction of nitrite production in macrophages. We have shown that chicken fibroblasts and macrophages possess a microbiostatic capacity once they are able to prevent the otherwise unchecked intracellular replication of Eimeria tenella following activation with culture supernatants identified as containing a strong IFN-gamma activity.
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PMID:Inhibition of Eimeria tenella development in vitro mediated by chicken macrophages and fibroblasts treated with chicken cell supernatants with IFN-gamma activity. 964 14

During pregnancy, trophoblast cells of the placenta contact maternal immune cells and yet are protected from attack. One mechanism that may account for this is that trophoblasts show altered expression of major histocompatibility complex (MHC) antigens. The gene for human leukocyte antigen G (HLA-G), a nonclassical gene, is expressed at high levels in trophoblast. Unlike other MHC class I genes, the HLA-G gene lacks an interferon (IFN) response element. Moreover, we demonstrate here that IFN, which regulates classical MHC class I genes in other cell types, does not affect these genes in trophoblast, owing to inactivation of an IFNalpha signaling pathway. Trophoblast cells (JEG-3 and JAR) were found to be selectively refractory to IFN. Specifically, although IFNalpha induced the transcription factors STAT1, STAT2, and IFN regulatory factor-1, and a protective response against encephalomyocarditis virus, it failed to protect the cells from vesicular stomatitis virus, activate a transfected MHC class I gene promoter, and induce the transcription factor IFN-stimulated gene factor (ISGF)-3. The lack of ISGF3 DNA-binding activity apparently was due to diminished p48/ISGF3gamma subunit activity since ISGF3 DNA-binding activity and IFNalpha induction of MHC class I promoter activity were reconstituted by p48/ISGF3gamma supplementation. These data indicate that a specific IFN signaling pathway is inactive in JEG-3 trophoblast cells because of altered activity of p48/ISGF3gamma, and they suggest IFN insensitivity as a mechanism that may help promote feto-placental survival.
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PMID:Defective induction of the transcription factor interferon-stimulated gene factor-3 and interferon alpha insensitivity in human trophoblast cells. 991 96

Antibody and cytotoxic T-lymphocyte (CTL) responses have critical roles in eliminating many viral infections. In addition to stimulation of the T-cell receptor, T cells require costimulatory signals to respond optimally. We evaluated the role of B7 costimulatory molecules (B7-1 and B7-2) in the immune response to viral infection using vesicular stomatitis virus (VSV) and mice lacking either B7-1 or B7-2 or both molecules. Mice lacking both B7-1 and B7-2 had essentially no anti-VSV immunoglobulin G1 (IgG1) response, decreased IgG2a responses, and normal IgM responses, while mice lacking either B7-1 or B7-2 had unaltered anti-VSV antibody responses compared to wild-type mice. Depletion of CD4(+) cells further reduced the IgG2a response in mice lacking both B7 molecules, suggesting that CD4(-) cells may supply help for IgG2a in the absence of B7 costimulation. The absence of both B7 molecules profoundly reduced generation of both primary and secondary VSV-specific class I major histocompatibility complex (MHC)-restricted CTL, whereas VSV-specific CTL responses in mice lacking either B7-1 or B7-2 were similar to those of wild-type animals. Class I MHC-restricted CTL in wild-type mice were not dependent on CD4(+) cells, suggesting that the failure of CTL in the absence of B7s is due to a lack of B7 costimulation directly to the CD8(+) CTL. These data demonstrate that B7-1 and B7-2 have critical, overlapping functions in the antibody and CTL responses to this viral infection.
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PMID:B7 costimulation is critical for antibody class switching and CD8(+) cytotoxic T-lymphocyte generation in the host response to vesicular stomatitis virus. 1059 Jan 7

The proteasome generates exact major histocompatibility complex (MHC) class I ligands as well as NH2-terminal-extended precursor peptides. The proteases responsible for the final NH2-terminal trimming of the precursor peptides had, until now, not been determined. By using specific selective criteria we purified two cytosolic proteolytic activities, puromycin-sensitive aminopeptidase and bleomycin hydrolase. These proteases could remove NH2-terminal amino acids from the vesicular stomatitis virus nucleoprotein cytotoxic T cell epitope 52-59 (RGYVYQGL) resulting, in combination with proteasomes, in the generation of the correct epitope. Our data provide evidence for the existence of redundant systems acting downstream of the proteasome in the antigen-processing pathway for MHC class I molecules.
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PMID:Two new proteases in the MHC class I processing pathway. 1106 1

Peptide fragments of self-proteins bound to major histocompatibility complex molecules within the thymus are important for positively selecting T cell receptor (TCR)-bearing CD4(+)CD8(+) double positive (DP) thymocytes for further maturation. The relationship between naturally processed thymic self-peptides and TCR-specific cognate peptides is unknown. Here we employ HPLC purification of peptides released from H-2K(b) molecules of the C57BL/6 thymus in conjunction with mass spectrometry (MS) and functional profiling to identify a naturally processed K(b)-bound peptide positively selecting the N15 TCR specific for the vesicular stomatitis virus octapeptide (VSV8) bound to K(b). The selecting peptide was identified in 1 of 80 HPLC fractions and shown by tandem MS (MS/MS) sequencing to correspond to residues 68-75 of the MLRQ subunit of the widely expressed mitochondrial NADH ubiquinone oxidoreductase (NUbO(68-75)). Of note, the peptide differs at six of its eight residues from the cognate peptide VSV8 and functions as a weak agonist for mature CD8 single positive (SP) N15 T cells, with activity 10,000-fold less than VSV8. In N15 transgenic (tg) recombinase activating gene 2(-/)- transporter associated with antigen processing 1(-/)- fetal thymic organ culture, NUbO(68-75) induces phenotypic and functional differentiation of N15 TCR bearing CD8 SP thymocytes. Failure of NUbO(68-75) to support differentiation of a second K(b)-restricted TCR indicates that its inductive effects are not general.
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PMID:A naturally processed mitochondrial self-peptide in complex with thymic MHC molecules functions as a selecting ligand for a viral-specific T cell receptor. 1158 11

In vivo priming of cytotoxic T lymphocytes (CTL) by DNA injection predominantly occurs by antigen transfer from DNA-transfected cells to antigen-presenting cells. A rational strategy for increasing DNA vaccine potency would be to use a delivery system that facilitates antigen uptake by antigen-presenting cells. Exogenous antigen presentation through the major histocompatibility complex (MHC) class I-restricted pathway of some viral antigens is increased after adequate virus-receptor interaction and the fusion of viral and cellular membranes. We used DNA-based immunization with plasmids coding for human immunodeficiency virus type 1 (HIV-1) Gag particles pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) to generate Gag-specific CTL responses. The presence of the VSV-G-encoding plasmid not only increased the number of mice displaying anti-Gag-specific cytotoxic response but also increased the efficiency of specific lysis. In vitro analysis of processing confirmed that exogenous presentation of Gag epitopes occurred much more efficiently when Gag particles were pseudotyped with the VSV-G envelope. We show that the VSV-G-pseudotyped Gag particles not only entered the MHC class II processing pathway but also entered the MHC class I processing pathway. In contrast, naked Gag particles entered the MHC class II processing pathway only. Thus, the combined use of DNA-based immunization and nonreplicating pseudotyped virus to deliver HIV-1 antigen to the immune system in vivo could be considered in HIV-1 vaccine design.
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PMID:Enhanced presentation of major histocompatibility complex class I-restricted human immunodeficiency virus type 1 (HIV-1) Gag-specific epitopes after DNA immunization with vectors coding for vesicular stomatitis virus glycoprotein-pseudotyped HIV-1 Gag particles. 1209 67

Characterizing peptide epitopes targeted by major histocompatibility complex (MHC)-restricted T cells of unknown specificity would have broad implications. In this article we introduce and validate an original phage-displayed library of noncovalent complexes of peptide and MHC (P/MHC). We show that soluble MHC molecules associate with peptides presented by a phage, thereby resulting in the formation of multivalent P/MHC phages. Complex formation is stabilized by the interaction of the soluble partner (MHC) with two components, peptide and beta2-microglobulin, both of which are covalently linked to the phage. As proof of concept, we have used this strategy to express peptide libraries in the context of H-2K(b). Using monoclonal antibody 25D (specific for ovalbumin/H-2K(b)) as a template to screen the library, we were able to select a variant epitope functionally and structurally related to the wild-type peptide. Interaction studies between monoclonal antibody 25D and cells suggest that the variant peptide has been selected on the basis of a decreased dissociation rate between the peptide/H-2K(b) complex and its ligand. A weak agonist of the N15 TCR (vesicular stomatitis virus/H-2K(b)-specific) was also isolated from another P/MHC library. This strategy opens up new perspectives for antigen discovery and the manipulation of T cell responses.
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PMID:Phage-displayed libraries of peptide/major histocompatibility complexes. 1476 65

Generation of CD8 T-cell responses to pathogens and tumors requires optimal expression of class I major histocompatibility complex/peptide complexes, which, in turn, is dependent on host cellular processing events and subject to interference by pathogens. To create a stable structure that is more immunogenic and resistant to immune evasion pathways, we have engineered class I molecules as single-chain trimers (SCTs), with flexible linkers connecting peptide, beta2m, and heavy chain. Herein we extend our earlier studies with SCTs to the K(b) ligand derived from vesicular stomatitis virus (VSV) to characterize further SCTs as probes of immune function as well as their potential in immunotherapy. The VSVp-beta2m-K(b) SCTs were remarkably stable at the cell surface, and immunization with DNA encoding SCTs elicited complex-specific antibody. In addition, SCTs were detected by cytotoxic T-lymphocytes specific for the native molecule, and the covalently bound peptide was highly resistant to displacement by exogenous peptide. SCTs can also prime CD8 T-cells in vivo that recognize the native molecule. Furthermore, SCTs were resistant to downregulation by the immune evasion protein mK3 of gamma herpesvirus 68. Moreover, owing to their preassembled nature, SCTs should be resistant to other immune evasion proteins that restrict peptide supply. Thus, SCTs possess therapeutic potential both for prophylactic treatment and for the treatment of ongoing infection.
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PMID:Applications of major histocompatibility complex class I molecules expressed as single chains. 1610 63


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