Tcellreceptor

The T cell receptor (TCR) is a cell-surface protein on T lymphocytes that recognizes antigens presented by major histocompatibility complex (MHC) molecules. Most T cells express an αβ TCR, which binds peptide–MHC complexes to guide adaptive immune responses. A minority of T cells express γδ TCRs, which can recognize a broader range of antigens, including some non-peptide molecules, without classical MHC restriction.

Structure and components: The TCR is a heterodimer, most commonly formed by α and β chains, though γ and δ chains can pair in some T cells. Each chain has variable and constant regions, with the variable regions forming the antigen-binding site. The TCR associates non-covalently with the CD3 signaling complex (CD3 γε, CD3εδ, and CD3ζζ) to transduce activation signals. The co-receptors CD4 or CD8 bind MHC class II or class I, respectively, helping stabilize the interaction and recruit signaling kinases.

Diversity and development: TCR diversity is generated by somatic recombination of V, (D), and J gene segments (V(D)J recombination), junctional diversity, and pairing of chains. Developing T cells undergo selection in the thymus: positive selection preserves cells capable of recognizing self-MHC, while negative selection eliminates those with strong self-reactivity, shaping a self-tolerant repertoire.

Function and signaling: Engagement of the TCR with peptide–MHC triggers intracellular signaling via ITAMs on CD3 and ζ chains, recruiting kinases such as Lck and ZAP-70 and leading to T cell activation, proliferation, and effector functions. Full activation typically requires co-stimulatory signals (for example, CD28–B7 interaction).

Clinical relevance: TCR recognition underpins adaptive immunity, vaccines, and autoimmunity. TCR-engineered T cells are used in experimental cancer therapies, and alterations in TCR signaling are targets for immunomodulatory drugs.