TcellActivation

T cell activation is the process by which naive T cells become activated in response to antigen exposure, enabling clonal expansion and differentiation into effector and memory cells. Activation begins when a T cell receptor (TCR) recognizes a peptide bound to major histocompatibility complex (MHC) on an antigen-presenting cell (APC), typically a dendritic cell, macrophage, or B cell. The TCR signal is enhanced by co-receptors (CD4 or CD8) that bind the same peptide–MHC complex.

A second signal is required for full activation: a co-stimulatory interaction, most notably CD28 on T cells engaging B7-1 (CD80) or B7-2 (CD86) on APCs. Adhesion molecules such as LFA-1–ICAM-1 strengthen the contact and stabilize the immunological synapse. Without co-stimulation, T cells may become anergic or undergo peripheral tolerance.

Intracellular signaling involves kinases such as Lck and ZAP-70, leading to activation of adaptor proteins LAT and SLP-76 and downstream pathways that raise intracellular calcium and activate transcription factors including NFAT, NF-κB, and AP-1. This drives transcription of interleukin-2 (IL-2) and other cytokines, fueling autocrine proliferation and differentiation.

The outcome of activation is clonal expansion and differentiation into effector and memory T cells. CD4+ helper T cells differentiate into subsets (e.g., Th1, Th2, Th17, Tfh, Treg) based on cytokine cues, while CD8+ T cells differentiate into cytotoxic T lymphocytes that can kill infected or abnormal cells. Regulation includes inhibitory receptors such as CTLA-4 and PD-1, and activation-induced cell death to limit responses.

T cell activation typically occurs in secondary lymphoid organs, with effector functions deployed at sites of infection and long-term memory established for rapid responses upon re-exposure.