Most alpha/beta T cell receptor diversity is due to terminal deoxynucleotidyl transferase.
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/beta 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 degrees / degrees mice, TCRAV diversity is one order of magnitude lower than the TCRBV diversity. In Tdt degrees / degrees animals, TCRBV chain diversity is reduced 10-fold compared with wild-type mice. In addition, in Tdt degrees / degrees mice, one BV chain can associate with three to four AV chains as in wild-type mice. The alpha/beta repertoire size in Tdt degrees / degrees mice is estimated to be 10(5) distinct receptors, approximately 5-10% of that calculated for wild-type mice. Thus, while Tdt activity is not involved in the combinatorial diversity resulting from alpha/beta pairing, it contributes to at least 90% of TCRalpha/beta diversity.
Cabaniols
J P
JP
Unité de Biologie Moléculaire du Gène, Institut National de la Sante et de la Recherche Medicale U277, Institut Pasteur, 75 724 Paris, France.
Fazilleau
N
N
Casrouge
A
A
Kourilsky
P
P
Kanellopoulos
J M
JM
D000818:Animals; D004253:DNA Nucleotidylexotransferase / Q000235:genetics / Q000502:physiology*; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D004253:DNA Nucleotidylexotransferase