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Cellular and molecular mechanisms of naive T-cell priming
Kramářová, Ilona ; Musil, Jan (advisor) ; Pačes, Jan (referee)
T cell priming is a complicated signalling process involving several levels of molecular and spatiotemporal regulation. Whether TCR signalling is initiated depends on the TCR signalling threshold which is thought to be set during the T cell development in thymus by CD5 and CD6. TCR intrinsic downstream signalling ("Signal 1") involves several pathways which result in the production of the main proinflammatory transcription factors, namely NF-κB, NFAT and AP-1. Those transcription factors participate in the transcription of proinflammatory cytokines such as IL-2. The molecular interface of T cell priming involves signalling from several types of costimulatory receptors, namely CD28, CD27 and HVEM, which are allocated to the immunological synapse. A significant overlap is present between the downstream signalling networks of TCR and costimulatory molecules which amplifies the transcription of proinflammatory genes. Shortly after T cell priming, coinhibitory molecules, namely CTLA-4 and PD-1, are upregulated to deliver negative signals to tune the stimulatory signalling. The interplay between costimulatory and coinhibitory molecules represents "Signal 2" that is responsible for further progression of T cell signalling. Key words T cell priming, TCR signalling, T cell costimulation, T cell...
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