Abstract:T cells play essential roles in adaptive immunity, and the specific recognition of antigens by T cell receptors (TCRs) is key in initiating anti-tumor and antiviral immune responses. Recent studies demonstrated that force plays an important regulatory role in T cell immune responses, laying the foundation for the emerging field of mechanoimmunology. In this review, we focus on the mechanisms by which force assists TCRs in distinguishing between specific antigens and non-specific antigens, as well as the critical role force plays in initiating TCR transmembrane signaling and triggering T cell activation. We summarize novel biophysical single-molecule tools and advanced imaging techniques that can deeply reveal the importance of mechanical forces at the molecular and/or cellular level. Here, we tried to provide a deeper understanding of the cutting-edge hotspots in the field of mechanoimunology and suggest potential future directions .