The Journal of Experimental Medicine
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Published 5 November 2001. doi:10.1084/jem.194.9.1385
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© Rockefeller University Press, 0022-1007/2001/11/1385/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 9, November 5, 2001 1385-1390

Brief Definitive Report

Most {alpha}/ß T Cell Receptor Diversity Is Due to Terminal Deoxynucleotidyl Transferase

Jean-Pierre Cabaniols, Nicolas Fazilleau, Armanda Casrouge, Philippe Kourilsky and Jean M. Kanellopoulos

Unité de Biologie Moléculaire du Gène, Institut National de la Sante et de la Recherche Medicale U277, Institut Pasteur, 75 724 Paris, France

Address correspondence to J.M. Kanellopoulos, Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, 25 rue du docteur Roux, 75 724 Paris, France. Phone: 33-1-45-68-85-49; Fax: 33-1-45-68-85-48; E-mail: jkanel{at}pasteur.fr

The contribution of template-independent nucleotide addition to antigen receptor diversity is unknown. We therefore determined the size of the T cell receptor (TCR){alpha}/ß repertoire in mice bearing a null mutation on both alleles of the terminal deoxynucleotidyl transferase (Tdt) gene. We used a method based upon polymerase chain reaction amplification and exhaustive sequencing of various AV-AJ and BV-BJ combinations. In both wild-type and Tdt°/° mice, TCRAV diversity is one order of magnitude lower than the TCRBV diversity. In Tdt°/° animals, TCRBV chain diversity is reduced 10-fold compared with wild-type mice. In addition, in Tdt°/° mice, one BV chain can associate with three to four AV chains as in wild-type mice. The {alpha}/ß repertoire size in Tdt°/° mice is estimated to be 105 distinct receptors, ~5–10% of that calculated for wild-type mice. Thus, while Tdt activity is not involved in the combinatorial diversity resulting from {alpha}/ß pairing, it contributes to at least 90% of TCR{alpha}/ß diversity.

Key Words: T cell repertoire • T cell receptor • knockout mice • terminal deoxynucleotidyl transferase • CDR3


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