T cell activation

Project leader: Monika Wolkers

An effective immune system is required to fight bacterial and viral infections. When a person is infected, immune cells recognize pathogen-specific structures that lead to immune activation.

The recognition of these pathogen-derived structures results in massive production of cytokines that kill the pathogen. In addition, the activated dendritic cells that recognized the pathogen initiate T cell responses to pathogen-specific antigens, which is required to clear the pathogen in later stages of infection. How effective these T cell responses are depends on the signals provided during T cell priming. Interestingly, the generation and maintenance of long-term T cell immunity is also dictated by the quality of these initial signals. Therefore, proficient activation of DCs and provision of the appropriate signals during T cell priming is required to protect us from recurring infections.

 

We address three major aspects of the immune activation:

• We aim to identify novel pathogen-specific patterns - in particular bacterial nucleic acid sequences - that lead to the immune activation of Dendritic Cells. We will focus on the molecular mechanisms that lead to the recognition of these bacterial structures.
• We study the molecular regulation of effector molecules that are produced by activated Dendritic Cells. Specifically we have focused on the cell-death inducing molecule TRAIL.
• We study how long-term T cell immunity is generated. In particular we want to identify the molecular mechanisms that allow memory T cells to swiftly act upon reinfections by producing massive amounts of cytokines.

Gaining insight in these processes should help us better understand how efficient immunity is developed against pathogens, and how vaccination strategies can be manipulated to achieve the most effective protection.