T-cell activation/proliferation pathway

The T-cell activation and proliferation pathway is a fundamental biological process that governs the expansion and effector function of T lymphocytes in response to antigenic stimuli [1]. It is initiated by the interaction of the T-cell receptor (TCR) with an antigen-major histocompatibility complex (MHC), supplemented by essential co-stimulatory signals such as the CD28-B7 interaction [2]. These events trigger complex intracellular signaling cascades involving kinases like Lck and ZAP-70, which lead to the activation of key transcription factors including NFAT, NF-κB, and AP-1 [3]. This transcriptional program drives the expression of interleukin-2 (IL-2) and its high-affinity receptor (CD25), creating an autocrine loop critical for the subsequent clonal expansion and differentiation of T cells [4]. In clinical practice, this pathway is a primary therapeutic focus; immunosuppressive drugs like cyclosporine and tacrolimus inhibit calcineurin to prevent T-cell activation in organ transplantation, while checkpoint inhibitors like pembrolizumab enhance T-cell activity to treat various malignancies [5, 6].

Other names

T-cell signaling pathwayT-cell receptor signaling pathwayLymphocyte activation processT-cell activation cascade

Modulation of T-cell signaling cascades, including inhibition of calcineurin, mTOR, or co-stimulatory molecules to suppress immunity, or blockade of inhibitory checkpoints (PD-1/CTLA-4) to enhance immune responses [5, 6].