Peptide FEA

The TCR receptor complex is an octomeric complex of variable TCR receptor α and β chains with three dimeric signaling modules CD3δ/ε, CD3γ/ε and CD247 ζ/ζ or ζ/η. Ionizable residues in the transmembrane domain of each subunit form a polar network of interactions that hold the complex together. Since the cytoplasmic tail of the TCR is extremely short, making it unlikely to participate in signaling, these signaling molecules are vital in propagating the signal from the triggered TCR into the cell. Each T cell expresses clonal TCRs which recognize specific peptide/MHC complex during physical contact between T cell and antigen-presenting cell-APC (MHC class II) or any other cell type (MHC class I) High on-rate and off-rate is characteristic for TCR and peptide/MHC interaction at physiological temperature. TCRs have very high degree of antigen specificity, despite of fact that the affinity to the peptide/MHC ligand is in the micromolar range. This weak binding between TCR and peptide/MHC was determined by the surface plasmon resonance (SPR) to be in the range 1-100 μM, the association constant in the range from 1000 to 10000 M⁻¹s⁻¹, The TCR affinity for peptided/MHC has a direct impact on modulation of T-cell function. T cells are very sensitive to their antigens despite the low affinity of TCR for its peptide/MHC and low numbers of specific peptide/MHC on the surface of target cells. The specific and efficient signaling via TCR might be regulated by dynamic oligomerization into TCR microclusters on the surface of T cells. In this scenario, T-cell sensitivity to antigen could be increased via avidity-based mechanism. The antigen sensitivity is higher in antigen-experienced T cells than in naive T cells. Naive T cells pass through the process of functional avidity maturation with no change in affinity. It is based on the fact that effector and memory (antigen-experienced) T cell are less dependent on costimulatory signals and higher antigen concentration than naive T cell.