Projektbeschreibung
Analyse immunologischer Mechanismen, die für die Impfstoffentwicklung bedeutend sind
Dendritische Zellen sind die professionellen antigenpräsentierenden Zellen des Immunsystems und verfügen über die inhärente Fähigkeit, Infektionen im Körper zu erkennen und die T-Zell-Immunantwort zu steuern. Das Ziel des EU-finanzierten Projekts plasTCD ist es, die Mechanismen zu beleuchten, mit denen dendritische Zellen die Antwort von Gedächtnis-T-Zellen bei einer zweiten Konfrontation mit einem Pathogen steuern. Die Arbeit wird sich um Influenza-Epitope drehen. Die Forschenden verwenden verschiedene phänotypische und funktionelle Ansätze, um die antigen-spezifischen wiederholten T-Zell-Antworten als Folge der Stimulierung durch dendritische Zellen zu charakterisieren. Die Ergebnisse werden bedeutende Informationen über die Kommunikation zwischen dendritischen Zellen und T-Zellen enthalten, mit direkten Auswirkungen auf die Impfstoff- und Immuntherapieentwicklung.
Ziel
The human immune system has the ability to fight various infectious diseases or self-cells turning malignant. Dendritic cells (DCs) are innate immune sensors and professional antigen presenting cells that initiate the development of adaptive immune responses towards the formation of memory cells. Very important studies deciphered the various signals in DCs to effectively polarize naïve T cells. However, a significant gap of knowledge remains on how DCs can mediate and influence antigen-specific T cell recall responses.
In this program, we aim to investigate how the different human DC subsets can modulate antigen-specific T cell recall responses directed against influenza (Flu) epitopes. To this end, we have designed a set of highly integrated work packages:
WP1: Using a systematic experimental approach of challenging co-cultures of pure DCs (6 different subsets) and Flu-specific T cells from healthy subjects, we will generate a functional atlas revealing the impact of the different DC subsets on antigen-specific T cell recall responses. T cell response status will be assessed at the protein level using phenotypic and functional approaches on multimer positive T cells.
WP2: Using CITE-seq technology together with cutting-edge system biology platforms, we will interrogate the transcriptomic programs and molecular pathways associated with antigen-specific T cell recall responses following stimulation with the various DC subsets.
WP3: As a complementary analysis of the data generated in WP2, we will perform TCR repertoire analysis to compare the clonal composition of the responding antigen-specific T cells.
This program represents an ambitious and promising project that will generate novel biological insights into fundamental immunological mechanisms of human DC-T cell communication. Such information could have direct clinical impact on the design of therapeutic DC-based vaccines, immunotherapies targeting DCs or T cell expansion protocols for adoptive transfer therapy
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenza
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensors
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Koordinator
75654 Paris
Frankreich