Dynamics in protein translation sustaining T cell preparedness.

Area of Science:

• Immunology
• Molecular Biology
• Cellular Biology

Background:

• Naive T cells must rapidly transition from quiescence to activation upon encountering pathogenic threats.
• The precise molecular mechanisms governing this rapid T cell activation are not fully understood.
• Understanding these mechanisms is crucial for developing effective immune therapies.

Purpose of the Study:

• To investigate the dynamics of mRNA translation and protein turnover in human naive and activated T cells.
• To identify molecular components and processes enabling rapid T cell activation.
• To provide a comprehensive dataset on T cell protein synthesis and turnover.

Main Methods:

• Utilized a pulsed stable isotope labeling by amino acids in cell culture (SILAC) approach.
• Analyzed mRNA translation kinetics and protein turnover rates in both naive and activated human T cells.
• Quantified ribosome occupancy and identified repressed mRNA species.

Main Results:

• Discovered that transcription factors maintaining T cell quiescence exhibit high turnover, facilitating their rapid depletion upon activation.
• Identified a significant pool of idling ribosomes and 242 repressed mRNA species in naive T cells.
• Revealed a reservoir of glycolytic enzymes in naive T cells that are rapidly engaged upon stimulation.
• Demonstrated an immediate translational and glycolytic switch crucial for T cell activation.

Conclusions:

• Naive T cells maintain a "prepared state" through readily accessible translational machinery and repressed mRNAs.
• This preparedness allows for an immediate and robust immune response upon encountering pathogens.
• The study provides valuable insights and data resources for understanding T cell activation and immune responses.