NKG2A inhibits TH2 cell effector function in vitro

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Analysis of Epitopes on Dengue Virus Envelope Protein Recognized by Monoclonal Antibodies and Polyclonal Human Sera by a High Throughput Assay

Dengue virus is the leading cause of arboviral diseases worldwide. The envelope protein is the major target of neutralizing antibodies and vaccine development. While previous studies have reported several epitopes on envelope protein, the possibility of interdomain epitopes and the relationship of epitopes to neutralizing potency remain unexplored. We developed a high throughput dot blot assay by using 67 alanine mutants of surface-exposed envelope residues as a systematic approach to identify epitopes recognized by mouse monoclonal antibodies and polyclonal human sera. Our results suggested the presence of interdomain epitopes more frequent than previously appreciated. Compared with monoclonal antibodies generated by traditional protocol, the potent neutralizing monoclonal antibodies generated by a new protocol showed several unique features of their epitopes. Moreover, the predominant epitopes of antibodies against envelope protein in polyclonal sera can be identified by this assay. These findings have implications for future development of epitope-specific diagnostics and epitope-based dengue vaccine, and add to our understanding of humoral immune responses to dengue virus at the epitope level

The Development of Therapeutic Antibodies That Neutralize Homologous and Heterologous Genotypes of Dengue Virus Type 1

Antibody protection against flaviviruses is associated with the development of neutralizing antibodies against the viral envelope (E) protein. Prior studies with West Nile virus (WNV) identified therapeutic mouse and human monoclonal antibodies (MAbs) that recognized epitopes on domain III (DIII) of the E protein. To identify an analogous panel of neutralizing antibodies against DENV type-1 (DENV-1), we immunized mice with a genotype 2 strain of DENV-1 virus and generated 79 new MAbs, 16 of which strongly inhibited infection by the homologous virus and localized to DIII. Surprisingly, only two MAbs, DENV1-E105 and DENV1-E106, retained strong binding and neutralizing activity against all five DENV-1 genotypes. In an immunocompromised mouse model of infection, DENV1-E105 and DENV1-E106 exhibited therapeutic activity even when administered as a single dose four days after inoculation with a heterologous genotype 4 strain of DENV-1. Using epitope mapping and X-ray crystallographic analyses, we localized the neutralizing determinants for the strongly inhibitory MAbs to distinct regions on DIII. Interestingly, sequence variation in DIII alone failed to explain disparities in neutralizing potential of MAbs among different genotypes. Overall, our experiments define a complex structural epitope on DIII of DENV-1 that can be recognized by protective antibodies with therapeutic potential

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Rôle du bec chez les volailles. Conséquences du débecquage

National audienceDebeaking is the cut of a part of the beak of domestic birds. The amount of beak tissue cut and the age at debeaking modulate the consequences of debeaking on poultry behaviour. The beak is essential to the bird for feed particle prehension, exploration of the environment, preening and social defense. It is an efficient tool. Beak epiderm contains dermal pappillae which play an important role in precise tactile discrimination. Debeaking the chicken reduces the input of sensorial information and leads to the formation of neuroma (abnormal and painfull proliferation of nervous tissues at the cutting point). However if birds are debeaked earlier than ten day old, both neuroma formation and pain are reduced. Debeaking can induce pain but also a reduction of sensorial perception. Debeaking reduces food intake and the efficiency of prehension feed particles by the bird. This reduces growth in debeaked chickens. However a debeaking effect on laying performances is still controversial. The major long term effect of debeaking on bird’s behaviour is inaction. Some floor raised birds (turkeys, layers...) require debeaking in practice to limit feather pecking and cannibalism. Choosing a housing system which excludes cages might limit the possibility to suppress mutilation of the beak, the chicken’s major contact with its environment.Le débecquage est l’ablation d’une partie du bec. Ses conséquences varient en fonction de la quantité de tissu enlevé et de l’âge auquel il a été réalisé. Le bec des volailles est un outil indispensable à la prise des particules alimentaires, à l’exploration de l’environnement, au toilettage corporel et à la défense sociale. Le bec est un outil efficace. L’épiderme du bec de poulet contient des papilles dermiques qui jouent un rôle important dans les discriminations tactiles fines. Le débecquage conduit à des pertes d’informations sensorielles en provenance du bec et à la formation de névromes (hyperplasies douloureuses des cylindraxes des nerfs amputés). Si le débecquage est effectué avant l’âge de 10 jours, la formation de névromes est limitée et la douleur reste faible. Le débecquage peut induire de la douleur, mais aussi une diminution de la perception sensorielle. Le débecquage a pour effet zootechnique principal une diminution de la consommation alimentaire et de l’efficacité mécanique de la prise de nourriture. Ceci s’accompagne d’une réduction du gain de poids chez les animaux débecqués. L’effet du débecquage sur les performances de ponte reste très controversé. A long terme, le principal effet du débecquage sur le comportement des poules est l’inactivité. Le débecquage est nécessaire en pratique pour certaines volailles élevées au sol (dindons, poules..), car il permet une réduction du cannibalisme et du picage des plumes. Le choix d’une technique d’élevage excluant les cages risque de limiter les possibilités réelles de supprimer la mutilation du bec des volailles, leur principal contact avec le monde extérieur

Integrated modelling of clean coal power cycles

URN 00/1426: part of the Cleaner Coal Technology ProgrammeAvailable from British Library Document Supply Centre-DSC:3291.521(273) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo