This review discusses the mechanisms of T cell activation, focusing on the T cell antigen receptor (TCR) signaling pathway. It begins with a historical overview of the TCR's discovery and its role in T cell signaling. The TCR complex includes the antigen-binding αβ chains and the CD3 proteins, which are essential for signal transduction. The CD3 proteins contain immunoreceptor tyrosine-based activation motifs (ITAMs) that become phosphorylated upon TCR engagement, leading to the recruitment of ZAP-70 and subsequent signaling events. The TCR signaling pathway involves the activation of src family tyrosine kinases, which phosphorylate ITAMs and recruit ZAP-70. This leads to the activation of downstream signaling pathways, including those involving PLCγ1, which generates second messengers such as IP3 and DAG. These second messengers trigger intracellular calcium release and activation of protein kinase C (PKC), which are essential for T cell activation. The review also discusses the role of costimulatory molecules like CD28 in enhancing T cell activation by providing additional signals that counteract anergy. The TCR signaling pathway is complex and involves multiple steps, including the activation of various kinases, the formation of signaling complexes, and the regulation of cytoskeletal dynamics. The review highlights the importance of these signaling events in T cell function and the ongoing research to fully understand the mechanisms of T cell activation.This review discusses the mechanisms of T cell activation, focusing on the T cell antigen receptor (TCR) signaling pathway. It begins with a historical overview of the TCR's discovery and its role in T cell signaling. The TCR complex includes the antigen-binding αβ chains and the CD3 proteins, which are essential for signal transduction. The CD3 proteins contain immunoreceptor tyrosine-based activation motifs (ITAMs) that become phosphorylated upon TCR engagement, leading to the recruitment of ZAP-70 and subsequent signaling events. The TCR signaling pathway involves the activation of src family tyrosine kinases, which phosphorylate ITAMs and recruit ZAP-70. This leads to the activation of downstream signaling pathways, including those involving PLCγ1, which generates second messengers such as IP3 and DAG. These second messengers trigger intracellular calcium release and activation of protein kinase C (PKC), which are essential for T cell activation. The review also discusses the role of costimulatory molecules like CD28 in enhancing T cell activation by providing additional signals that counteract anergy. The TCR signaling pathway is complex and involves multiple steps, including the activation of various kinases, the formation of signaling complexes, and the regulation of cytoskeletal dynamics. The review highlights the importance of these signaling events in T cell function and the ongoing research to fully understand the mechanisms of T cell activation.