TCRs

The T cell receptor (TCR) is the antigen recognition molecule on T lymphocytes. The conventional TCR (alpha-beta TCR) is composed of an alpha chain and beta chain (each ~40 kDa), disulfide-linked together and non-covalently associated with the CD3 complex (gamma, delta, epsilon chains) and zeta chains (homodimer or heterodimer). Together, these form the TCR-CD3 complex. Each T cell expresses ~50,000 copies of identical TCR molecules. TCR diversity is generated by V(D)J recombination, theoretically allowing recognition of > 10^15 different antigens. The TCR does NOT directly recognize free antigen but recognizes peptide-MHC complexes on the surface of other cells (MHC restriction). This is a fundamental principle of T cell immunity: CD8+ T cells recognize peptide-MHC Class I, and CD4+ T cells recognize peptide-MHC Class II. When TCR engages peptide-MHC and receives co-stimulation (CD28-B7 interaction), the T cell becomes activated and differentiates. Alternative gamma-delta TCRs are found on a small subset of T cells (particularly in epithelial tissues) and recognize different antigens (non-MHC-restricted). TCR expression defines T cell lineage; absence of TCR beta chain indicates thymic failure (DiGeorge syndrome).