TCRKomplex

TCRKomplex is the multi-subunit receptor complex expressed on the surface of most T lymphocytes that mediates antigen recognition and initiates T cell signaling. It consists of two main parts: the T cell receptor (TCR) heterodimer, usually TCRαβ or TCRγδ, which binds peptide antigens presented by major histocompatibility complex (MHC) molecules, and the CD3 signaling complex, composed of CD3γ, CD3δ, CD3ε, and the CD3ζ (CD247) chain. The CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails, which transduce signals following receptor engagement. The CD3ζ chain typically provides a high density of ITAMs that amplify signaling.

Activation begins when the TCR recognizes a peptide–MHC complex, with the CD4 or CD8 co-receptors often stabilizing the interaction and recruiting the Src-family kinase Lck to phosphorylate ITAMs. This phosphorylation recruits and activates the tyrosine kinase ZAP-70, leading to a signaling cascade involving LAT, SLP-76, PLC-γ1, calcium mobilization, and downstream transcription factors such as NFAT, NF-κB, and AP-1. The TCRKomplex does not signal alone; co-receptor engagement and intracellular signaling molecules coordinate full activation and clonal expansion.

In humans, αβ T cells comprise the majority of the repertoire, while γδ T cells use alternative TCR chains but rely on the same CD3 signaling apparatus. Abnormal TCRKomplex signaling can contribute to immunodeficiency, autoimmunity, or altered responses to infection and transplantation. The complex is a central target of immunomodulatory therapies that affect T cell activation.