AG-PROCESSING BY DC · Identification of cellular proteins involved in uptake and cross-presentation of pathogen-derived proteins by professional antigen presenting cells
6РП — Действия „Мария Кюри“
- Период
- 2006-02-01 → 2008-01-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Дендритните клетки поемат протеини от патогени и ги представят на повърхността си, за да активират имунната система. Разбирането на този процес помага да се разбере как тялото разпознава и елиминира инфекциозните агенти.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - AG-PROCESSING BY DC (Identification of cellular proteins involved in uptake and cross-presentation of pathogen-derived proteins by ... antigen presenting cells)
The main aim of this grant was the reintegration of the recipient, who had made her career in science mainly outside the European Union, into her country of origin. Immediately prior to the start of this grant, the recipient moved to the University of Utrecht in the Netherlands, to (re-) establish a research group there. Focus of research since then has been the elucidation of pathways via which pathogen-derived proteins are processed by the host, in order to mount a protective immune response. Dendritic cells, which are professional antigen presenting cells, are known to play an essential role in this process. In specific, DC phagocytose pathogen-derived proteins and display these in the context of MHC class I on their cell surface. In this way, they can interact with naive pathogen-specific CD8 T cells that then become activated, leading to clearance of the infecting agent. One still unelucidated step in the processing of such phagocytosed antigens remains the route by which the antigens enter the class I antigen processing pathway, which usually starts in the cytosol (nucleus). In order to unravel this pathway in further detail, we performed a functional genomic screen. A siRNA library was introduced into bone marrow-derived stem cells, that were then differentiated into DC, and the ability of these DC to present a model antigen was analyzed. Our asays showed that DC, belonging to one specific subset that is known to croos-present phagocytosed antigens, actually consisted of again different subsets with very different capabilities to cross-present. Our future experiments aim to further define these subsets, and the early events following antigen uptake that protect antigens from degradation in the phagosome and allow them to enter the cytosol. During the project period, the recipient applied for and acquired several grants from different funding agencies. Her group presently consists of several PhD students, a post doc and a technician and focuses on antigen processing and T cell responses to infectious agents.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
The proposer is an accomplished investigator who has spent six years in the US and wishes to return to her home country. Over the years, the research of the proposer has focused on the MHC-I antigen-processing pathway in infected cells and dendritic cells (DC) and on CD8 T cell priming. The main objective of this proposal is to obtain funding to help the proposer to return to and reintegrate into her home country and to establish a research group there.The research project: The induction of protective CD 8 T-cell responses against intracellular pathogens requires that DC internalise pathogen-derived proteins (antigens) and process these into small peptides. Such peptides, presented by MHC-I molecules on the DC surface, will activate antigen-specific CD8 T-cells to eliminate infected cells. So far, the cellular mechanisms involved in antigen uptake and processing for cross-presentation" by uninfected DC remain poorly understood.This project aims to identify proteins that play a role i n antigen cross-presentation. We will use a lentivirus-expressed small interfering (si)RNA library that targets 34.000 mouse genes to silence the expression of single genes in hematopoietic stem cells that will be differentiated into DC. These DC will be tested for their capacity to cross-present antigens and DC that lack cross-presenting activity will be sorted using multi-colour flow-cytometry. siRNAs expressed in the purified DC will be identified by micro-array analysis. The function of the so identified gene products will be analysed using transfectant cell lines that express siRNA constructs of interest.We expect to identify different categories of proteins that are essential for antigen presentation on DC and, thereby, to unravel the MHC-I antigen-processing pathway that operates in DC to present ingested antigens. The elucidation of the cellular mechanisms involved in antigen cross-presentation may help the rational design of effective CD8 T-cell-inducing vaccines."
Оригинален текст от CORDIS (на английски).
Участници
- FACULTY OF VETERINARY MEDICINE, UNIVERSITY OF UTRECHT · UTRECHTКоординаторНиво градНидерландия
Връзки
Данни: CORDIS, © Европейски съюз