Alpha-beta T cell receptors (TCRs) are antigen specific receptors, which are essential to the immune response and are present on the cell surface of T lymphocytes. They recognize peptide-loaded major histocompatibility complexes (pMHCs), that are displayed by antigen presenting cells (APCs). Binding of alpha-beta TCR to pMHC initiates TCR-CD3 clustering on the cell surface and intracellular activation of LCK, that phosphorylates the ITAM motifs of CD3gamma, CD3delta, CD3epsilon and CD3zeta, enabling the recruitment of ZAP70. In turn, ZAP70 phosphorylates LAT, which recruits numerous signaling molecules to form the LAT signalosome. The LAT signalosome propagates signal branching to three major signaling pathways, the calcium signaling, the mitogen-activated protein kinase (MAPK) kinase and the nuclear factor NFkappaB (NF-kB) pathways, leading to the mobilization of transcription factors, that are critical for gene expression and essential for T cell growth and differentiation. The T cell repertoire is generated by V-D-J-C rearrangements. This repertoire is then shaped by intrathymic selection events to generate a peripheral T cell pool of self-MHC restricted, non-autoaggressive T cells. Post-thymic interaction of alpha-beta TCRs with the pMHCs shapes TCR structural and functional avidity.
