Abstract
The short splice variant of mouse terminal deoxynucleotidyl transferase (TdTS) catalyzes the addition of nontemplated nucleotides (N addition) at the coding joins of B cell and T cell antigen receptor genes. However, the activity and function of the long isoform of TdT (TdTL) have not been determined. We show here, in vitro and in vivo, that TdTL is a 3′→5′ exonuclease that catalyzes the deletion of nucleotides at coding joins. These findings suggest that the two TdT isoforms may act in concert to preserve the integrity of the variable region of antigen receptors while generating diversity.
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Acknowledgements
We thank S. Gilfillan and D. Mathis for the TdTL and TdTS cDNA clones; D. J. Mazure and F. W. Perrino for hTREX2; M. Oettinger for full-length RAG-1 and RAG-2; L. Gartland for FACS; X. Y. Liu for technical assistance; M. A. Anderson, D. S. Nelson, P. D. Burrows for helpful discussions; and A. Brookshire for preparing this manuscript. Supported by NIH grants AI 523133, AI 07051, AI36420 and the Howard Hughes Medical Institute (D. B. R.).
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Thai, TH., Purugganan, M., Roth, D. et al. Distinct and opposite diversifying activities of terminal transferase splice variants. Nat Immunol 3, 457–462 (2002). https://doi.org/10.1038/ni788
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DOI: https://doi.org/10.1038/ni788
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