Priming of CD8 + T Cell Responses to Liver Stage Malaria Parasite Antigens

While the role of malaria parasite-specific memory CD8(+) T cells in the control of exo-erythrocytic stages of malaria infection is well documented and generally accepted, a debate is still ongoing regarding both the identity of the anatomic site where the activation of naive pathogen-specific T cells is taking place and contribution of different antigen-presenting cells (APCs) into this process. Whereas some studies infer a role of professional APCs present in the lymph nodes draining the site of parasite injection by the mosquito, others argue in favor of the liver as a primary organ and hepatocytes as stimulators of naïve parasite-specific T cell responses. This review aims to critically analyze the current knowledge and outline new lines of research necessary to understand the induction of protective cellular immunity against the malaria parasite

Detection and defect correction of operating process

The article is devoted to the current problem of enterprise competitiveness rise in hard and competitive terms of business environment. The importance of modern equipment for detection of defects and their correction is explained. Production of chipboard is used as an object of research. Short description and main results of estimation efficiency of innovative solutions of enterprises are considered

Thermodynamic similarity of stacked-cup multiwall carbon nanotubes and graphite

When conducting photo elicitation interviews (PEI), researchers introduce photographs into the interview context. Although PEI has been employed across a wide variety of disciplines and participants, little has been written about the use of photographs in interviews with children. In this article, the authors review the use of PEI in a research study that explored the perspectives on camp of children with cancer. In particular, they review some of the methodological and ethical challenges, including (a) who should take the photographs and (b) how the photographs should be integrated into the interview. Although some limitations exist, PEI in its various forms can challenge participants, trigger memory, lead to new perspectives, and assist with building trust and rapport

CR2Cancer: a database for chromatin regulators in human cancer

Identification of Master Regulators (MRs) during cancer development contributes greatly to the design of novel targeted therapy. However, it is challenging to trace the MR that regulate the gene signature (e.g. differentially expressed genes) derived from a limited number of transcriptome profiles. The main reason is that the targets (collectively termed as regulon) of MRs in cancer type-specific context is not available for enrichment analysis in the signature. To this aim, we generated the regulon of MRs using high throughput omics data from The Cancer Genome Atlas (TCGA), and developed a web server MR4Cancer, which can prioritize MRs driving phenotypic differentiation of interest in 26 cancer types. Based on the input gene list or expression profiles, it outputs six groups of ranked MRs, including transcription regulators, miRNAs, recurrently mutated genes, kinases, phosphatases, and hubs from protein-protein interaction network. Simultaneously, Gene Ontology and canonical pathway analyses are also conducted to further elucidate the function of MR candidates. Moreover, our tool presents dynamic network visualization for MR-target relations, and users can interactively customize it as high quality figures for their publications. We expect this user-friendly and powerful web application will provide researchers new insights into carcinogenesis and therapeutic intervention.published_or_final_versio

A straw tube detector for the PANDA experiment

The PANDA experiment will be built at the FAIR facility in Darmstadt (Germany) to perform accurate tests of the strong interaction through pp and pA annihilations. This paper will address the design issue of the Straw Tube Tracker (STT), one of the two options proposed for the PANDA Central Tracker

Targeting of EBNA1 for rapid intracellular degradation overrides the inhibitory effects of the Gly-Ala repeat domain and restores CD8+T cell recognition

Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) includes a unique glycine-alanine repeat domain that inhibits the endogenous presentation of cytotoxic T lymphocyte (CTL) epitopes through the class I pathway by blocking proteasome-dependent degradation of this antigen. This immune evasion mechanism has been implicated in the pathogenesis of EBV-associated diseases. Here, we show that cotranslational ubiquitination combined with N-end rule targeting enhances the intracellular degradation of EBNA1, thus resulting in a dramatic reduction in the half-life of the antigen. Using DNA expression vectors encoding different forms of ubiquitinated EBNA1 for in vivo studies revealed that this rapid degradation, remarkably, leads to induction of a very strong CTL response to an EBNA1-specific CTL epitope. Furthermore, this targeting also restored the endogenous processing of HLA class I-restricted CTL epitopes within EBNA1 for immune recognition by human EBV-specific CTLs. These observations provide, for the first time, evidence that the glycine-alanine repeat-mediated proteasomal block on EBNA1 can be reversed by specifically targeting this antigen for rapid degradation resulting in enhanced CD8+ T cell-mediated recognition in vitro and in vivo

Defining the expression hierarchy of latent T-cell epitopes in Epstein-Barr virus infection with TCR-like antibodies

Epstein-Barr virus (EBV) is a gamma herpesvirus that causes a life-long latent infection in human hosts. The latent gene products LMP1, LMP2A and EBNA1 are expressed by EBV-associated tumors and peptide epitopes derived from these can be targeted by CD8 Cytotoxic T-Lymphocyte (CTL) lines. Whilst CTL-based methodologies can be utilized to infer the presence of specific latent epitopes, they do not allow a direct visualization or quantitation of these epitopes. Here, we describe the characterization of three TCR-like monoclonal antibodies (mAbs) targeting the latent epitopes LMP1[subscript 125–133], LMP2A[subscript 426–434] or EBNA1[subscript 562–570] in association with HLA-A0201. These are employed to map the expression hierarchy of endogenously generated EBV epitopes. The dominance of EBNA1[subscript 562–570] in association with HLA-A0201 was consistently observed in cell lines and EBV-associated tumor biopsies. These data highlight the discordance between MHC-epitope density and frequencies of associated CTL with implications for cell-based immunotherapies and/or vaccines for EBV-associated disease

Epstein Barr Virus-Encoded EBNA1 Interference with MHC Class I Antigen Presentation Reveals a Close Correlation between mRNA Translation Initiation and Antigen Presentation

Viruses are known to employ different strategies to manipulate the major histocompatibility (MHC) class I antigen presentation pathway to avoid recognition of the infected host cell by the immune system. However, viral control of antigen presentation via the processes that supply and select antigenic peptide precursors is yet relatively unknown. The Epstein-Barr virus (EBV)-encoded EBNA1 is expressed in all EBV-infected cells, but the immune system fails to detect and destroy EBV-carrying host cells. This immune evasion has been attributed to the capacity of a Gly-Ala repeat (GAr) within EBNA1 to inhibit MHC class I restricted antigen presentation. Here we demonstrate that suppression of mRNA translation initiation by the GAr in cis is sufficient and necessary to prevent presentation of antigenic peptides from mRNAs to which it is fused. Furthermore, we demonstrate a direct correlation between the rate of translation initiation and MHC class I antigen presentation from a certain mRNA. These results support the idea that mRNAs, and not the encoded full length proteins, are used for MHC class I restricted immune surveillance. This offers an additional view on the role of virus-mediated control of mRNA translation initiation and of the mechanisms that control MHC class I restricted antigen presentation in general