Organization and Rearrangement of TCR loci
The adaptive immune response in vertebrates relies on the expression of antigen-specific receptors on lymphocytes to recognize a myriad of different molecules produced by pathogens and cancer cells. The antigen T-cell receptor (TCR) genes are organized in complex genetic loci composed of multiple gene segments that can be found in two possible configurations during the maturation of T-cell precursors in the thymus, unrearranged and rearranged, the latter necessary for expression of a functional TCRαβ or TCRγδ, and the generation of T lymphocytes. The transition from an unrearranged to a rearranged genomic configuration depends on an irreversible somatic gene segment recombination process, termed V(D)J recombination. This chapter describes the genomic organization of human and mouse TCR loci and summarizes our current knowledge about how intrathymic signals direct changes in the activity and conformation of TCR locus chromatin that are essential for the formation of TCR repertoires.
