LymphoAtlas

LymphoAtlas provides a time-resolved, high-resolution phosphoproteomic resource that identifies, quantifies, and characterizes phosphorylation dynamics across thousands of sites in primary T cells during the first 10 minutes after T-cell receptor (TCR) stimulation.

Key Features:

• Time-resolved high-resolution phosphoproteomics: Maps phosphorylation events across thousands of sites with temporal resolution within the first 10 minutes after TCR engagement.
• Bioinformatic integration: Applies bioinformatic analyses to interpret datasets and reveal regulation of cytoskeletal remodeling, transcription, translation, and metabolic pathways in response to TCR activation.
• Functional module identification: Identifies functional modules mobilized within seconds of TCR engagement.
• Regulatory protein identification and validation: Detects phosphorylation-regulated adaptor proteins such as ITSN2 and links their phosphorylation to modulation of T-cell effector functions, with validation using a fast-track gene inactivation approach.

Scientific Applications:

• Signaling network reconstruction: Enables decoding of complex TCR signaling networks in primary T cells.
• Mechanistic studies and target discovery: Supports studies of immune response mechanisms and identification of potential therapeutic targets in autoimmune diseases and vaccine development.
• Functional genomics and intervention: Facilitates pinpointing regulatory proteins like ITSN2 to enable targeted interventions in modulating T-cell functions.

Methodology:

Time-resolved high-resolution mass spectrometry following TCR stimulation generated phosphoproteomic data that were subjected to bioinformatic analysis to identify phosphorylation sites and their temporal dynamics.