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As the amount of biomedical information available in the literature continues to increase, databases that aggregate this information continue to grow in importance and scope. The population of databases can occur either through fully automated text mining approaches or through manual curation by human subject experts. We here report our experiences in populating the National Institute of Allergy and Infectious Diseases sponsored Immune Epitope Database and Analysis Resource ( IEDB, http://iedb.org), which was created in 2003, and as of 2012 captures the epitope information from approximately 99% of all papers published to date that describe immune epitopes (with the exception of cancer and HIV data). This was achieved using a hybrid model based on automated document categorization and extensive human expert involvement. This task required automated scanning of over 22 million PubMed abstracts followed by classification and curation of over 13 000 references, including over 7000 infectious disease-related manuscripts, over 1000 allergy-related manuscripts, roughly 4000 related to autoimmunity, and 1000 transplant/alloantigen-related manuscripts. The IEDB curation involves an unprecedented level of detail, capturing for each paper the actual experiments performed for each different epitope structure. Key to enabling this process was the extensive use of ontologies to ensure rigorous and consistent data representation as well as interoperability with other bioinformatics resources, including the Protein Data Bank, Chemical Entities of Biological Interest, and the NIAID Bioinformatics Resource Centers. A growing fraction of the IEDB data derives from direct submissions by research groups engaged in epitope discovery, and is being facilitated by the implementation of novel data submission tools. The present explosion of information contained in biological databases demands effective query and display capabilities to optimize the user experience. Accordingly, the development of original ways to query the database, on the basis of ontologically driven hierarchical trees, and display of epitope data in aggregate in a biologically intuitive yet rigorous fashion is now at the forefront of the IEDB efforts. We also highlight advances made in the realm of epitope analysis and predictive tools available in the IEDB. [ABSTRACT FROM AUTHOR]

Interferon-γ (IFN-γ) is an important cytokine which regulates inflammatory and immune response mechanisms. IFN-γ enhances the presentation and recognition of antigens by inducing the expression of major histocompatibility complex (MHC) proteins, by activating effector T cells and mononuclear phagocytes, and by modulating immunoglobulin production and class selection in B cells. Inappropriate production of IFN-γ has been implicated in the pathogenesis of several autoimmune and inflammatory diseases and in graft rejection. Here, we describe, a recombinant inhibitor of IFN-γ, termed murine IFN-γ receptor immunoadhesin (mIFN-γR-IgG). We constructed this immunoadhesin by linking the extracellular portion of the mouse IFN-γR to the hinge and Fc region of an IgG1 heavy chain. Murine IFN-γR-IgG is secreted by transfected cells as a disulphide-bonded homodimer which binds IFN-γ bivalently, with high affinity and in a species-specific manner. In vitro, mIFN-γRIgG can block mIFN-γ-induced antiviral activity and expression of the class I MHC antigen H-2Kk in cultured cells. In vivo, mIFN-γ,R-IgG can block the function of endogenous mIFN-γ in mouse models of infection with Listeria monocytogenes and of contact sensitivity. These results show that mIFNγR-IgG is an effective and specific inhibitor of mIFN-γ both in vitro and in vivo. Thus, in general, IFN-γ receptor immunoadhesins may be useful for investigating the biological functions of IFN-γ as well as for preventing deleterious effects of IFN-γ in human disease. [ABSTRACT FROM AUTHOR]

Splenic B cells from older MRL/ Mp-lpr/lpr (MRL/1) and male BXSB mice responded to 2-mercaptoethanol (2-ME) in in vitro culture and generated immunoglobulin-secreting cells (IgSC). Optimal concentration of 2-ME to induce IgSC was 5 x 10-5 M. Kinetic studies revealed that the generation of IgSC was already apparent after 24 hr of culture and peak response was attained on the 2nd day. The response of B cells to 2-ME was enhanced in the presence of splenic T cells. Irradiation of B cells reduced the generation of IgSC. The B cell population of autoimmune mice responding to 2-ME to generate IgSC seems to be in a terminal stage of differentiation. This increased B cell differentiation was characteristic of autoimmune mice and assumed to have some significance in the development of autoimmune diseases. [ABSTRACT FROM AUTHOR]