The role of short homology repeats and TdT in generation of the invariant gamma delta antigen receptor repertoire in the fetal thymus.
Fetal thymic and adult epithelial V gamma 3+ and V gamma 4+ T cells express gamma delta antigen receptors (TCR) with invariant junctions lacking N nucleotides. Using transgenic recombination substrates, we show that di- or trinucleotide repeats, either in the coding region or in P elements, have strong effects on the site of recombination. In other mice bearing a terminal deoxynucleotidyl transferase (TdT) transgene under the control of the CD2 promoter, we found that the frequency of canonical junctions was markedly reduced with a concomitant increase in in-frame noncanonical junctions with N nucleotides. Together, our results show that short homology repeats direct the site of rearrangement and thus play a critical role in the generation of gamma delta T cell receptor canonical junctions. Increased TdT activity in V gamma 3+ T cells has a inhibitory effect on junctional homogeneity in these cells.
Zhang
Y
Y
Department of Molecular and Cellular Biology, University of California, Berkeley 94720, USA.
Cado
D
D
Asarnow
D M
DM
Komori
T
T
Alt
F W
FW
Raulet
D H
DH
Allison
J P
JP
D000818:Animals; D001483:Base Sequence; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000276:immunology; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D004253:DNA Nucleotidylexotransferase