Most α/β T cell receptor diversity is due to terminal deoxynucleotidyl transferase

JP Cabaniols, N Fazilleau, A Casrouge… - The Journal of …, 2001 - rupress.org
JP Cabaniols, N Fazilleau, A Casrouge, P Kourilsky, JM Kanellopoulos
The Journal of experimental medicine, 2001rupress.org
The contribution of template-independent nucleotide addition to antigen receptor diversity is
unknown. We therefore determined the size of the T cell receptor (TCR) α/β 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 …
The contribution of template-independent nucleotide addition to antigen receptor diversity is unknown. We therefore determined the size of the T cell receptor (TCR)α/β 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 α/β 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 α/β pairing, it contributes to at least 90% of TCRα/β diversity.
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