Terminal Deoxynucleotidyl Transferase(TdT)

AbstractTerminal deoxynucleotidyl transferase (TdT) is a DNA polymerase with the unique capacity to add nucleotides to a DNA strand in an untemplated fashion. This capacity is specifically utilised in developing B‐cells and T‐cells in vertebrates to generate extra diversity in the antigen receptor repertoire. During the process of V(D)J recombination developing B‐ and T‐cell rearrange the DNA encoding the immunoglobulin (Ig) and T‐cell receptor (TCR) genes, respectively. Following the introduction of double‐strand DNA breaks and prior to the ligation by members of the nonhomologous end joining (NHEJ) pathway, TdT can add nontemplated (N‐)nucleotides to the open DNA ends. Through the capacity to generate longer junctions with new nucleotide compositions, TdT is critical in driving the generation of the enormous antigen receptor repertoire with a potential 1015unique sequences that facilitate recognition of the diverse range of pathogens vertebrates are exposed to.Key ConceptsTdT is a DNA polymerase with nontemplated activity.TdT adds random nucleotides in the junctional region during V(D)J recombination.TdT expression is tightly regulated in early B‐ and T‐cell progenitors.Detection of nuclear TdT expression using recombinant antibodies is an important biomarker for diagnostics and minimal residual disease monitoring of acute leukaemias.TdT expression is regulated by IL‐7 receptor signalling.Foetal B‐ and T‐cell progenitors have reduced TdT expression and function.