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1.
Med Trop (Mars) ; 72 Spec No: 66-71, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22693932

RESUMEN

The outbreak of chikungunya that occurred on French Island territories in the southwest Indian Ocean in 2005 and 2006 caused severe morbidity and mortality. In the aftermath, French authorities set up a scientific task force including experts in epidemiology, public health, entomology, virology, immunology, sociology, animal health, community and hospital medicine. The mission of the task force was to conceive and propose research programs needed to increase understanding of the disease and epidemic and to help public health officials in improving epidemic response measures. The purpose of this article is to describe the findings of the task force at the end of its two-year existence and initial outcomes in the the areas studied. Discussion emphasizes topics requiring further study.


Asunto(s)
Infecciones por Alphavirus/prevención & control , Control de Enfermedades Transmisibles/organización & administración , Brotes de Enfermedades/prevención & control , Grupo de Atención al Paciente/organización & administración , Aedes/fisiología , Aedes/virología , Infecciones por Alphavirus/epidemiología , Animales , Fiebre Chikungunya , Ensayos Clínicos como Asunto , Francia/epidemiología , Humanos , Islas del Oceano Índico/epidemiología , Biología Molecular
2.
J Proteome Res ; 9(7): 3527-36, 2010 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-20459142

RESUMEN

Innate immunity has evolved complex molecular pathways to protect organisms from viral infections. One pivotal line of cellular defense is the induction of the antiviral effect of interferon. To circumvent this primary response and achieve their own replication, viruses have developed complex molecular strategies. Here, we provide a systems-level study of the human type I interferon system subversion by the viral proteome, by reconstructing the underlying protein-protein interaction network. At this network level, viruses establish a massive and a gradual attack, from receptors to transcription factors, by interacting preferentially with highly connected and central proteins as well as interferon-induced proteins. We also demonstrate that viruses significantly target 22% of the proteins directly interacting with the type I interferon system network, suggesting the relevance of our network-based method to identify new candidates involved in the regulation of the antiviral response. Finally, based on the comparative analysis of interactome profiles across four viral families, we provide evidence of common and differential targeting strategies.


Asunto(s)
Interacciones Huésped-Patógeno/inmunología , Interferón Tipo I/inmunología , Mapeo de Interacción de Proteínas/métodos , Biología de Sistemas/métodos , Virus/inmunología , Bases de Datos Genéticas , Flaviviridae/inmunología , Herpesviridae/inmunología , Humanos , Papillomaviridae/inmunología , Retroviridae/inmunología , Transducción de Señal , Estadísticas no Paramétricas
3.
Nucleic Acids Res ; 38(Database issue): D371-8, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20007148

RESUMEN

Large collections of protein-encoding open reading frames (ORFs) established in a versatile recombination-based cloning system have been instrumental to study protein functions in high-throughput assays. Such 'ORFeome' resources have been developed for several organisms but in virology, plasmid collections covering a significant fraction of the virosphere are still needed. In this perspective, we present ViralORFeome 1.0 (http://www.viralorfeome.com), an open-access database and management system that provides an integrated set of bioinformatic tools to clone viral ORFs in the Gateway(R) system. ViralORFeome provides a convenient interface to navigate through virus genome sequences, to design ORF-specific cloning primers, to validate the sequence of generated constructs and to browse established collections of virus ORFs. Most importantly, ViralORFeome has been designed to manage all possible variants or mutants of a given ORF so that the cloning procedure can be applied to any emerging virus strain. A subset of plasmid constructs generated with ViralORFeome platform has been tested with success for heterologous protein expression in different expression systems at proteome scale. ViralORFeome should provide our community with a framework to establish a large collection of virus ORF clones, an instrumental resource to determine functions, activities and binding partners of viral proteins.


Asunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas , Bases de Datos de Ácidos Nucleicos , Bases de Datos de Proteínas , Genes Virales , Sistemas de Lectura Abierta , Clonación Molecular , Biología Computacional/tendencias , Técnicas Genéticas , Genoma Viral , Almacenamiento y Recuperación de la Información/métodos , Internet , Estructura Terciaria de Proteína , Programas Informáticos , Interfaz Usuario-Computador
4.
Mol Syst Biol ; 4: 230, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18985028

RESUMEN

A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein-protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFbeta pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins.


Asunto(s)
Hepatitis C/metabolismo , Proteínas Virales/metabolismo , Hepacivirus/metabolismo , Hepacivirus/fisiología , Humanos , Unión Proteica , Técnicas del Sistema de Dos Híbridos
5.
J Virol ; 76(14): 6919-28, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12072493

RESUMEN

The presence of hepatitis C virus (HCV) RNA-containing particles in the low-density fractions of plasma has been associated with high infectivity. However, the nature of circulating HCV particles and their association with immunoglobulins or lipoproteins as well as the characterization of cell entry have all been subject to conflicting reports. For a better analysis of HCV RNA-containing particles, we quantified HCV RNA in the low-density fractions of plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated chronically HCV-infected patients. HCV RNA was always found in at least one of these fractions and represented 8 to 95% of the total plasma HCV RNA. Surprisingly, immunoglobulins G and M were also found in the low-density fractions and could be used to purify the HCV RNA-containing particles (lipo-viro-particles [LVP]). Purified LVP were rich in triglycerides; contained at least apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical particles with a diameter of more than 100 nm and with internal structures. Delipidation of these particles resulted in capsid-like structures recognized by anti-HCV core protein antibody. Purified LVP efficiently bind and enter hepatocyte cell lines, while serum or whole-density fractions do not. Binding of these particles was competed out by VLDL and LDL from noninfected donors and was blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the LDL receptor increased their internalization. These results suggest that the infectivity of LVP is mediated by endogenous proteins rather than by viral components providing a mechanism of escape from the humoral immune response.


Asunto(s)
Hepacivirus/patogenicidad , Lipoproteínas LDL/análisis , Lipoproteínas VLDL/análisis , ARN Viral/sangre , Virión/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Hepacivirus/fisiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/virología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lipoproteínas/análisis , Lipoproteínas IDL , Microscopía Electrónica , Células Tumorales Cultivadas , Virión/fisiología
6.
J Immunol ; 167(7): 3785-91, 2001 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11564795

RESUMEN

Proinflammatory oxidized phospholipids are generated during oxidative modification of low-density lipoproteins (LDL). The production of these proinflammatory oxidized phospholipids is controlled by secreted enzymes that circulate as proteins complexed with LDL and high-density lipoprotein. During the acute phase response to tissue injury, profound changes occur in lipoprotein enzymatic composition that alter their anti-inflammatory function. Monocytes may encounter oxidized phospholipids in vivo during their differentiation to macrophages or dendritic cells (DC). In this study we show that the presence of oxidized LDL (oxLDL) at the first day of monocyte differentiation to DC in vitro yielded phenotypically atypical cells with some functional characteristics of mature DC. Addition of oxLDL during the late stage of monocyte differentiation gave rise directly to phenotypically mature DC with reduced uptake capacity, secreting IL-12 but not IL-10, and supporting both syngeneic and allogeneic T cell stimulation. In contrast to known mediators of DC activation, oxLDL did not trigger maturation of immature DC. An intriguing possibility is that a burst of oxidized phospholipids is an endogenous activation signal for the immune system, which is tightly controlled by lipoproteins during the acute phase response.


Asunto(s)
Células Dendríticas/inmunología , Lipoproteínas LDL/farmacología , Monocitos/inmunología , Diferenciación Celular , Células Cultivadas , Células Dendríticas/citología , Endocitosis , Humanos , Inmunofenotipificación , Isoantígenos/inmunología , Activación de Linfocitos , Monocitos/citología , Monocitos/efectos de los fármacos , Receptores de Interleucina/biosíntesis , Receptores de Interleucina-12 , Linfocitos T/inmunología
7.
J Neuroimmunol ; 118(2): 233-44, 2001 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-11498258

RESUMEN

The capacity of interferon beta to alter the course of multiple sclerosis has promoted a new therapeutic concept, based upon the modulation of the immune response rather than its suppression. As the proteasome plays a crucial role in the control of the inflammatory process and immune cell survival, targeting the proteasome appears as a novel approach for the prevention and treatment of inflammatory autoimmune diseases. We have previously shown that ritonavir, an HIV-1 protease inhibitor used in AIDS therapy, can modulate the proteasome function by inhibiting the chymotrypsin-like activity and enhancing the trypsin-like activity. We have, therefore, explored its therapeutic potential on experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis, in Lewis rats and SJL mice. Daily administration of ritonavir during autoimmune antigen stimulation prevented clinical symptoms of EAE in a dose- and time-dependent manner. This protection was accompanied by an inhibition of the mononuclear cell infiltration into the central nervous system usually observed in EAE. Despite a complete absence of clinical symptoms during first EAE induction, ritonavir-treated animals became resistant to further induction of EAE, suggesting an immune mechanism of protection. These results suggest that proteasome modulation using ritonavir or analogues may be of interest for patients with multiple sclerosis.


Asunto(s)
Cisteína Endopeptidasas/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/prevención & control , Inhibidores de la Proteasa del VIH/farmacología , Complejos Multienzimáticos/efectos de los fármacos , Ritonavir/farmacología , Saquinavir/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Femenino , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos , Proteína Básica de Mielina , Complejo de la Endopetidasa Proteasomal , Ratas , Ratas Endogámicas Lew , Médula Espinal/patología
8.
J Virol Methods ; 95(1-2): 111-9, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11377718

RESUMEN

Real-time PCR technology may provide an accurate and sensitive method to quantify hepatitis C virus (HCV) RNA. So far, studies have been carried out using the Taqman technology with the ABI Prism 7700 sequence detector. An alternative and simple real-time PCR assay is described with no probe requirement, based on the SYBR Green I dye and LightCycler fluorimeter. Amplicon synthesis was monitored continuously by SYBR Green I dye binding to double stranded DNA during PCR of the 5' HCV non-coding (NC) region. Specificity was verified by amplicon melting temperatures. An external standard curve was constructed with serial 10 fold dilutions of a modified synthetic HCV 5' NC RNA. A wide range linear relationship (up to 3.7x10(9) copies/ml) was observed between number of PCR cycle needed to detect a fluorescent signal and number of RNA copy. Intra- and inter-assay coefficients of variation were 0.7 to 2.1 and 3.7% respectively, indicating good reproducibility of the method. Thirty-three HCV positive sera of different genotypes were quantified by this method and gave similar but more sensitive results compared to the branched DNA (bDNA) technology.


Asunto(s)
Hepacivirus/genética , ARN Viral/análisis , Fluorometría/métodos , Humanos , Reacción en Cadena de la Polimerasa/métodos , Reproducibilidad de los Resultados
10.
Proc Natl Acad Sci U S A ; 95(22): 13120-4, 1998 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-9789051

RESUMEN

Inhibitors of the protease of HIV-1 have been used successfully for the treatment of HIV-1-infected patients and AIDS disease. We tested whether these protease inhibitory drugs exerted effects in addition to their antiviral activity. Here, we show in mice infected with lymphocytic choriomeningitis virus and treated with the HIV-1 protease inhibitor ritonavir a marked inhibition of antiviral cytotoxic T lymphocyte (CTL) activity and impaired major histocompatibility complex class I-restricted epitope presentation in the absence of direct effects on lymphocytic choriomeningitis virus replication. A potential molecular target was found: ritonavir selectively inhibited the chymotrypsin-like activity of the 20S proteasome. In view of the possible role of T cell-mediated immunopathology in AIDS pathogenesis, the two mechanisms of action (i.e., reduction of HIV replication and impairment of CTL responses) may complement each other beneficially. Thus, the surprising ability of ritonavir to block the presentation of antigen to CTLs may possibly contribute to therapy of HIV infections but potentially also to the therapy of virally induced immunopathology, autoimmune diseases, and transplantation reactions.


Asunto(s)
Cisteína Endopeptidasas/metabolismo , Inhibidores de la Proteasa del VIH/farmacología , Coriomeningitis Linfocítica/tratamiento farmacológico , Coriomeningitis Linfocítica/inmunología , Complejos Multienzimáticos/metabolismo , Ritonavir/farmacología , Linfocitos T Citotóxicos/inmunología , Linfocitos T/inmunología , Animales , Genes MHC Clase I/efectos de los fármacos , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/enzimología , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Inmunidad Celular , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Complejo de la Endopetidasa Proteasomal , Ritonavir/uso terapéutico , Linfocitos T/efectos de los fármacos , Linfocitos T Citotóxicos/efectos de los fármacos
11.
J Exp Med ; 186(2): 269-78, 1997 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-9221756

RESUMEN

Despite the development of an efficient specific immune response during measles virus (MV) infection, an immunosuppression occurs contributing to secondary infections. To study the role of nucleocapsid protein (NP) in MV-induced immunosuppression, we produced recombinant MV NP. Purified recombinant NP exhibited biochemical, antigenic, and tridimensional structure similar to viral NP. By flow cytometry, we showed that viral or recombinant NP bound to human and murine B lymphocytes, but not to T lymphocytes. This binding was specific, independent of MHC class II expression, and dependent of the B lymphocyte activation state. The murine IIA1. 6 B cell line, deficient in the Fc receptor for IgG (FcgammaRII) expression, did not bind NP efficiently. Transfected IIA1.6 cells expressing either murine FcgammaRIIb1 or b2, or human FcgammaRIIa, b1*, or b2 isoforms efficiently bound NP. Furthermore, this binding was inhibited up to 90% by monoclonal antibodies 2.4G2 or KB61 specific for murine and human FcgammaRII, respectively. Finally, the in vitro Ig synthesis of CD40- or Ig-activated human B lymphocytes in the presence of interleukin (IL)-2 and IL-10 was reduced by 50% in the presence of recombinant NP. These data demonstrate that MV NP binds to human and murine FcgammaRII and inhibits in vitro antibody production, and therefore suggests a role for NP in MV-induced immunosuppression.


Asunto(s)
Formación de Anticuerpos , Linfocitos B/fisiología , Nucleoproteínas/fisiología , Receptores de IgG/fisiología , Proteínas Virales/fisiología , Animales , Células Cultivadas , Humanos , Tolerancia Inmunológica , Sarampión/inmunología , Ratones , Proteínas de la Nucleocápside , Receptores de Antígenos de Linfocitos B/fisiología
12.
Eur J Immunol ; 27(4): 855-9, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9130635

RESUMEN

Major histocompatibility complex (MHC) restriction of the immune response is established during positive selection of T cells in the thymus. This occurs mainly through interactions of T cell receptor of developing thymocytes with MHC/peptide ligands on cortical thymic epithelial cells (TEC). An ongoing controversy concerns the origin and the role of peptides involved in the positive selection of thymocytes. Evidence provided here shows that processing of MHC class II complexes in cortical TEC differs from that of medullary TEC. Removal of the invariant chain associated with MHC class II complexes was rapid and complete in medullary TEC which present peptides from both exogenous and cytosolic origin. In cortical TEC, a large fraction of class II dimers remained associated with a 10-12-kDa fragment of invariant chain (Ii). Incomplete removal of Ii correlated with the inability of cortical TEC to present peptides from exogenous origin. However, presentation of peptides from cytosolic proteins by cortical TEC remained possible. Thus, most peptides from exogenous proteins may be excluded from participating in positive selection of CD4+ T cells by a mechanism limiting Ii breakdown.


Asunto(s)
Presentación de Antígeno , Antígenos de Histocompatibilidad Clase II/inmunología , Timo/inmunología , Animales , Animales Recién Nacidos , Antígenos de Diferenciación de Linfocitos B/metabolismo , Línea Celular , Dimerización , Células Epiteliales , Epitelio/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Ratones , Ratones Endogámicos C57BL , Peso Molecular , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Timo/citología
13.
Int Immunol ; 9(4): 581-9, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-9138019

RESUMEN

Type II collagen (CII) is an arthritogenic self antigen in DBA/1 (H-2q) mice. To analyze the intracellular processing of this fibrillar protein in the context of I-Aq molecules, we have generated hybrid antigen-presenting cells (APC) by fusion of B lymphoma (A20 and M12) cells with CII-primed spleen cells from DBA/1 mice. Efficient presentation of CII by these APC to specific T cell hybridomas required prior cleavage of the antigen and intracellular handling of the peptides. Inhibition of protein transport by brefeldin A prevented the presentation of CII peptides to T cell hybridomas, indicating that the intracellular presentation of CII was dependent on neo-synthesis of I-Aq molecules. In contrast, exposure of hybrid B lymphomas to leupeptin, a protease inhibitor, induced a dose-dependent increase of CII-specific T cell response, while abrogating the I-Aq-restricted presentation of ovalbumin. The enhancing effect of leupeptin was also observed when immune B cells were used as APC. In contrast, leupeptin inhibited the presentation of CII peptides by macrophages or total spleen cells. Pulse-chase analysis of metabolically labeled hybrid APC and immunoprecipitation with antibodies specific for class II molecules or invariant (li) chain revealed that leupeptin did not affect the li chain processing or the formation of stable class II dimers. The stimulatory effect of leupeptin observed on CII presentation suggests that leupeptin protects CII epitopes by interfering with proteases involved in the intracellular degradation of CII.


Asunto(s)
Presentación de Antígeno/efectos de los fármacos , Colágeno/inmunología , Colágeno/metabolismo , Leupeptinas/farmacología , Animales , Células Presentadoras de Antígenos/enzimología , Células Presentadoras de Antígenos/inmunología , Antígenos de Diferenciación de Linfocitos B/metabolismo , Brefeldino A , Colágeno/efectos de los fármacos , Ciclopentanos/farmacología , Dimerización , Epítopos/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Inmunofenotipificación , Linfoma de Células B/inmunología , Linfoma de Células B/metabolismo , Ratones , Ratones Endogámicos DBA , Inhibidores de Proteasas/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Dodecil Sulfato de Sodio/farmacología , Células Tumorales Cultivadas
14.
J Biol Chem ; 272(50): 31348-54, 1997 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-9395464

RESUMEN

ApoC-III overexpression in mice results in severe hypertriglyceridemia due primarily to a delay in the clearance of triglyceride-rich lipoproteins. We have, in primary cultures of rat hepatocytes, characterized a lipolysis-stimulated receptor (LSR). The apparent number of LSR that are available on rat liver plasma membranes is negatively correlated with plasma triglyceride concentrations measured in the fed state. We therefore proposed that the primary physiological role of the LSR is to contribute to the cellular uptake of triglyceride-rich lipoproteins. We have now tested the effect of apoC-III on the binding of triglyceride-rich lipoproteins to LSR. Supplementation of 125I-very low density lipoprotein (VLDL) with apoC-III inhibited the LSR-mediated binding, internalization, and degradation of 125I-VLDL in primary cultures of rat hepatocytes. Studies using isolated rat liver plasma membranes showed that enrichment of human VLDL and chylomicrons with synthetic or purified human apoC-III decreased their binding to the LSR by about 40%. Supplementation of triglyceride-rich lipoproteins under the same conditions with human apoC-II had no such inhibitory effect, despite the fact that this apoprotein bound as efficiently as apoC-III to these particles. Preincubation of LDL with apoC-III did not modify its binding to LSR. Partitioning studies using 125I-apoC-III showed that this lack of effect was due to apoC-III's inability to efficiently associate with LDL. Purified human apoC-III1 was as efficient as the synthetic nonsialylated form of apoC-III in inhibiting binding of VLDL to LSR. However, despite a 2-fold greater binding of apoC-III2 to VLDL, this isoform was a less efficient inhibitor of the binding of VLDL to LSR than apoC-III1 or nonsialylated apoC-III. Desialylation of apoC-III2 by treatment with neuraminidase increased the inhibition of VLDL binding to LSR to a level similar to that observed with apoC-III1 and nonsialylated apoC-III. We propose that apoC-III regulates in part the rate of removal of triglyceride-rich particles by inhibiting their binding to the LSR, and that the level of inhibition is determined by the degree of apoC-III sialylation.


Asunto(s)
Apolipoproteínas C/química , Lipólisis , Lipoproteínas/metabolismo , Receptores de Lipoproteína/metabolismo , Animales , Apolipoproteína C-III , Células Cultivadas , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ácido Oléico/farmacología , Ratas , Ratas Sprague-Dawley , Triglicéridos/metabolismo
15.
Immunity ; 4(6): 545-53, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8673701

RESUMEN

Thymic epithelium is involved in negative selection, but its precise role in selecting the CD4 T cell repertoire remains elusive. By using two transgenic mice, we have investigated how medullary thymic epithelium (mTE) and bone marrow (BM)-derived cells contribute to tolerance of CD4 T cells to nuclear beta-galactosidase (beta-gal). CD4 T cells were not tolerant when beta-gal was expressed in thymic BM-derived cells. In contrast, CD4 T cells of mice expressing beta-gal in mTE were tolerized. Tolerance resulted from presentation of endogenous beta-gal by mTE cells but not from cross-priming. mTE cells presented nuclear beta-gal to a Th clone in vitro, while thymic dendritic cells did not. The data indicate that mTE but not thymic BM-derived cells can use a MHC class II endogenous presentation pathway to induce tolerance to nuclear proteins.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Tolerancia Inmunológica , Proteínas Nucleares/inmunología , Timo/inmunología , Animales , Presentación de Antígeno/genética , Células Epiteliales , Epitelio/inmunología , Centro Germinal/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Tolerancia Inmunológica/genética , Interleucina-2/farmacología , Activación de Linfocitos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Ratones Transgénicos , Proteínas Nucleares/genética , Proteínas Recombinantes/farmacología , Timo/anatomía & histología , beta-Galactosidasa/genética
18.
Cell ; 72(4): 635-48, 1993 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-7679955

RESUMEN

The invariant chain (li) has aroused much interest because of its close association with major histocompatibility complex (MHC) class II molecules. Various functions have been proposed for it; several of these have received experimental support, but most have not been definitively proven, owing largely to uncertainties inherent in the experimental systems employed. We have now generated a line of mice devoid of the invariant chain by introducing a drastic mutation into the li gene. Cells from mutant animals show aberrant transport of MHC class II molecules, resulting in reduced levels of class II complexes at the surface, and these do not have the typical compact conformation indicative of tight peptide binding. Consequently, mutant cells present protein antigens very poorly and mutant mice are deficient in producing and at negatively selecting CD4+ T cells.


Asunto(s)
Antígenos de Diferenciación de Linfocitos B , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Histocompatibilidad Clase II/fisiología , Inmunidad , Animales , Células Presentadoras de Antígenos/inmunología , Transporte Biológico , Membrana Celular/metabolismo , Epítopos , Técnica del Anticuerpo Fluorescente , Antígenos de Histocompatibilidad Clase II/ultraestructura , Ratones , Ratones Mutantes , Mutagénesis Insercional , Conformación Proteica , Linfocitos T/inmunología
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