T-cell activation is the central event in adaptive immunity, converting antigen recognition into clonal expansion and effector differentiation. The process begins when the T-cell receptor (TCR) engages a peptide-MHC complex on an antigen-presenting cell. The TCR itself lacks intrinsic catalytic activity and signals through the associated CD3 complex, whose immunoreceptor tyrosine-based activation motifs (ITAMs) become phosphorylated by the Src-family kinase Lck, which is recruited via the CD4 or CD8 coreceptor. Phosphorylated CD3 ITAMs create docking sites for the tyrosine kinase ZAP-70, which is itself activated by Lck and then phosphorylates downstream scaffolds. Foremost among these is the transmembrane adaptor LAT, whose phosphorylation nucleates a signaling complex that recruits and activates phospholipase C-gamma1 (PLC-gamma1). PLC-gamma1 hydrolyzes membrane phosphoinositides to generate diacylglycerol and inositol trisphosphate, triggering calcium flux and protein kinase C activation. The resulting calcium signal activates calcineurin, which dephosphorylates the transcription factor NFAT and permits its nuclear translocation to drive cytokine gene expression, including IL-2. Full, productive activation requires a second signal delivered through the costimulatory receptor CD28, which engages B7 ligands and amplifies and sustains signaling; in its absence, T cells become anergic. The early activation marker CD69 is rapidly induced upon stimulation and serves as a reliable readout of T-cell engagement and tissue retention. Defects or dysregulation in these proximal signaling events underlie immunodeficiencies, autoimmunity, and lymphoid malignancies, and the pathway is the basis for many immunomodulatory therapies. Probing the proximal signalosome requires reagents spanning receptors, kinases, adaptors, and transcription factors. This sampler pack brings together validated antibodies against CD3, CD28, Lck, ZAP-70, LAT, PLC-gamma1, NFAT, and CD69 for studying proximal TCR signaling and T-cell activation.