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)

The requirements for viral and host protein synthesis in the generation of target antigens for cytotoxic T lymphocytes (CTL) was evaluated by using vesicular stomatitis virus (VSV) inactivated by UV irradiation (UV-VSV). EL4 target cells incubated with UV-VSV were recognized and lysed by anti-VSV CTL, indicating that de novo synthesis of viral proteins was not required for the generation of antigens recognized by antiviral CTL. Anti-VSV CTL from H-2b mice primarily recognize determinants derived from the VSV N protein bound to the class I major histocompatibility complex (MHC) antigen H-2Kb. Comparison of a cloned CTL line representing this specificity and a heterogeneous population of anti-VSV CTL showed that determinants other than that recognized by the cloned CTL were generated more efficiently from UV-VSV. By using vaccinia virus recombinants that express deletion fragments of the N protein, it was shown that these additional determinants were probably derived from VSV proteins other than the N protein. The protein synthesis inhibitor emetine was used to determine whether newly synthesized host proteins were required for antigen generation. The addition of emetine to target cells prior to or at the time of the addition of UV-VSV inhibited lysis by anti-VSV CTL. This inhibition could be due to depletion of newly synthesized MHC molecules from intracellular membranes. This hypothesis was supported by using brefeldin A to delay membrane protein transport in target cells during the time of incubation with emetine and UV-VSV, which resulted in partial reversal of the effect of emetine. These results suggest that newly synthesized class I MHC molecules are required for the generation of antigens recognized by anti-VSV CTL.
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PMID:Role of de novo protein synthesis in target cells recognized by cytotoxic T lymphocytes specific for vesicular stomatitis virus. 165 79

The specificity of anti-vesicular stomatitis virus (VSV)-specific cytotoxic T cells was explored with cell lines expressing VSV genes introduced by electroporation. Low levels of nucleocapsid (N) protein were detected on the surface of VSV-infected cells, but N protein could not be detected on the plasma membrane of transfected EL4 cells. Intracellular N protein was detectable by enzyme-linked immunosorbent assay or immunoprecipitation in some of the transfected cell lines but not in others, unless the transfected genes were induced by sodium butyrate. However, all of the stably transfected EL4 cell lines expressing the VSV-Indiana N protein were efficiently lysed by serotype-specific and cross-reactive anti-VSV cytotoxic T cells (CTLs). Primary cross-reactive anti-VSV CTLs appeared to be specific solely for N protein, based on cold-target competition assays using infected and transfected target cells. Cell lines expressing 100- to 1,000-fold less N protein than did VSV-infected cells were efficiently lysed by both primary and secondary anti-VSV CTLs. Cell lines expressing 100-fold less G protein than did VSV-infected cells were not lysed by either population of effectors. Significantly, cold-target competition studies with secondary CTLs demonstrated that N protein-expressing cell lines were more efficient competitors than were VSV-infected cells even though the latter expressed 100- to 1,000-fold more N protein. This was not an artifact of viral infection since infection of the transfected cell lines did not affect their ability to compete. The possibility that cell lines constitutively expressing internal virus proteins present antigen more effectively than infected cells do is discussed.
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PMID:N protein is the predominant antigen recognized by vesicular stomatitis virus-specific cytotoxic T cells. 302 3

Cross-reactive recognition of alloantigen by "self + X"-reactive cytotoxic T lymphocytes (CTL) has been documented in a variety of systems. It has been shown previously that the H-2Kb-restricted CTL response of C57BL/6 (B6) mice to vesicular stomatitis virus (VSV) infection is partially cross-reactive on uninfected target cells expressing the H-2Kbm8 mutation. In this report, we describe the isolation and detailed characterization of such dual-reactive CTL. By employing EL4 tumor lines transfected with genes encoding various VSV proteins, we demonstrated that the majority of dual-reactive CTL recognize the internal N protein of VSV and are also reactive against uninfected bm8 targets. Although the response of normal B6 mice to bm8 stimulators shows no measurable cross-reactivity on VSV-infected targets, the response of VSV-primed B6 mice to bm8 stimulation is almost entirely cross-reactive, lysing VSV-B6 targets and uninfected bm8 targets roughly equally. Furthermore, about 70% of CTL clones isolated from such mice by bm8 stimulation are dual-reactive with respect to effector function. Analysis at the population and clonal levels with cold target competition and antibody blocking suggests that the bulk of dual-reactive CTL have a higher avidity for VSV-B6 targets than for bm8 targets. The extreme case of this is illustrated by a fraction of CTL clones, isolated and maintained on bm8 stimulators, which lyse VSV-B6 targets but do not lyse bm8 targets. One such CTL clone is shown to be specific for the bm8 antigen in proliferation assays. These results demonstrate that: the specificity of an alloreactive CTL response may be dramatically altered by previous antigenic encounters; and dual-reactive CTL display a significant difference in affinity of the CTL receptor-determinant interaction, depending on the target which is recognized.
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PMID:Characterization of dual-reactive H-2Kb-restricted anti-vesicular stomatitus virus and alloreactive cytotoxic T cells. 303 10

Carbohydrate antigens rarely provide target epitopes for cytotoxic T lymphocytes (CTL). Disialoganglioside GD2 is a glycolipid expressed at high levels in human tumors and a small group of murine lymphomas (EL4, RBL5, RMA, RMA-S, A13, and BALBRVE). Immunization of C57B1/6 mice with irradiated EL4 cells stimulated a specific CTL response and protected these animals from engraftment of EL4 lymphoma. The CTL activity resided in the CD4-CD8+ population, was dependent on T cell receptor alpha/beta, and was not removed by anti-natural killer cell immunoabsorption, but was restricted to GD2 and H-2b bearing targets. CTL activity could be completely inhibited by GD2-oligosaccharide-specific monoclonal antibodies and their F(ab')2 fragments, but not by immunoglobulin G3 myelomas or antibodies against GD3 or GM2. Soluble GD2 did not inhibit specific tumor lysis. RMA-S lymphoma cells (GD2+H-2b-TAP2 deficient) were resistant to GD2-specific CTL. Sialic acid-containing peptides eluted from EL4 lymphoma cells could (a) stabilize H-2 molecules on RMA-S cells and (b) sensitize them for GD2-specific CTL. Control peptides (derived from vesicular stomatitis virus nucleoprotein peptide and GD2-negative lymphomas) could also stabilize H-2 on RMA-S, but were resistant to GD2-specific CTL. These H-2-binding peptides could be purified by anti-GD2 affinity chromatography. We postulate a new class of naturally occurring epitopes for T cells where branched-chain oligosaccharides are linked to peptides with anchoring motifs for the major histocompatibility complex class I pocket. While analogous to the haptens trinitrophenyl and O-beta-linked acetyl-glucosamine, the potential implications of natural carbohydrates as antigenic epitopes for CTL in biology are considerable.
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PMID:GD2 oligosaccharide: target for cytotoxic T lymphocytes. 754 Jun 57

Oromucosal administration of murine interferon-alpha/beta (IFN-alpha/beta) or individual recombinant species of murine IFN-alpha, IFN-beta, or IFN-gamma or recombinant human IFN-alpha1-8, which is active in the mouse, exerted a marked antiviral activity in mice challenged systemically with a lethal dose of encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV), or varicella zoster virus (VZV). The effects observed were dose dependent and similar in magnitude to those observed following parenteral administration of the same dose of IFN. No antiviral activity was observed after oromucosal administration of murine IFN-alpha/beta in animals in which the IFN receptor had been inactivated by homologous recombination. In contrast to parenteral treatment, oromucosal IFN therapy was found to be ineffective when IFNs were administered before virus infection. Oromucosal administration of IFN-alpha also exerted a marked antitumor activity in mice injected i.v. with highly malignant Friend erythroleukemia cells or other transplantable tumors, such as L1210 leukemia, which has no known viral etiology, the EL4 tumor, or the highly metastatic B16 melanoma. These results show that high doses of IFN can be administered by the oromucosal route apparently without ill effect, raising the possibility that the oromucosal route will prove to be an effective means of administering high doses of IFN that are clinically effective but poorly tolerated.
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PMID:Oromucosal interferon therapy: marked antiviral and antitumor activity. 1009 Apr