Projektbeschreibung
Charakterisierung der T-Zell-Vielfalt
T-Zellen sind ein wichtiger Bestandteil der adaptiven Immunität gegen Krankheitserreger und umfassen verschiedene Populationen mit jeweils eigenen Funktionen. Eine Bestimmung dieser T-Zell-Untergruppen beruht meist auf der Oberflächenexpression von Antigenen, darunter CD4+ und CD8+. Doch uns fehlt das grundlegende Verständnis der funktionalen Vielfalt von T-Zellen auf Einzelzellebene. Es ist somit das zentrale Ziel des EU-finanzierten Projekts FunDiT, die Genexpressionsprofile zu charakterisieren und wichtige Pfade einzelner T-Zellen zu bestimmen. Die Projektergebnisse werden dazu beitragen, die Rolle der verschiedenen T-Zellen-Untergruppen bei der Immunantwort zu erkennen.
Ziel
T cells have a central role in most adaptive immune responses, including immunity to infection, cancer, and autoimmunity. Increasing evidence shows that even resting steady-state T cells form many different subsets with unique functions. Variable level of self-reactivity and previous antigenic exposure are most likely two major determinants of the T-cell diversity. However, the number, identity, and biological function of steady-state T-cell subsets are still very incompletely understood. Receptors to ligands from TNF and B7 families exhibit variable expression among T-cell subsets and are important regulators of T-cell fate decisions. We hypothesize that pathways triggered by these receptors substantially contribute to the functional diversity of T cells.The FunDiT project uses a set of novel tools to systematically identify steady-state CD8+ T cell subsets and characterize their biological roles. The project has three complementary objectives.
(1) Identification of CD8+ T cell subsets. We will identify subsets based on single cell gene expression profiling. We will determine the role of self and foreign antigens in the formation of these subsets and match corresponding subsets between mice and humans.
(2) Role of particular subsets in the immune response. We will compare antigenic responses of particular subsets using our novel model allowing inducible expression of a defined TCR. The activity of T-cell subsets in three disease models (infection, cancer, autoimmunity) will be characterized.
(3) Characterization of key costimulatory/inhibitory pathways. We will use our novel mass spectrometry-based approach to identify receptors and signaling molecules involved in the signaling by ligands from TNF and B7 families in T cells.
The results will provide understanding of the adaptive immunity in particular disease context and resolve long-standing questions concerning the roles of T-cell diversity in protective immunity and tolerance to healthy tissues and tumors.
Wissenschaftliches Gebiet
Schlüsselbegriffe
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Finanzierungsplan
ERC-STG - Starting GrantGastgebende Einrichtung
142 20 Praha 4
Tschechien