Regulation of the mature human T cell receptor gamma repertoire by biased V-J gene rearrangement.
To delineate how gene rearrangement influences the expressed human gamma delta T cell repertoire, we generated T cell receptor gamma (TCR gamma) V domain-specific cDNA libraries from the peripheral lymphocytes of eight donors and sequenced a total of 232 TCR gamma gene transcripts. The libraries consisted of both in-frame and out-of-frame rearranged TCR gamma genes. The in-frame TCR gamma gene transcripts were used to determine the diversity of functional T cells, whereas the out-of-frame transcripts, primarily derived from alpha beta T cells, were used to assess the frequencies of TCR V gamma-J gamma rearrangements in progenitor T lymphocytes. The results showed that both sets of transcripts exhibited strikingly restricted V gamma-J gamma combinations. Only 11 of 40 potential V gamma-J gamma rearrangements were common ( > or = 3% of total). The pattern of gene usage in the functional and nonfunctional transcripts was similar and did not differ markedly among donors. The only exception was the predominance of V gamma 9-JP in potentially functional transcripts from seven of eight individuals. These results show that V gamma-J gamma rearrangement is nonrandom and suggest that the diversity of TCR gamma genes in the functional gamma delta T cell repertoire partly depends upon preferentially rearranged V gamma-J gamma gene combinations. However, the expansion of V gamma 9/V gamma 2 T cells in adult peripheral blood can only be explained by antigenic selection of relatively rare V gamma 9-JP recombinants.
Kohsaka
H
H
Department of Medicine, University of California, San Diego, La Jolla 92093.
Chen
P P
PP
Taniguchi
A
A
Ollier
W E
WE
Carson
D A
DA
D000328:Adult; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016133:Polymerase Chain Reaction / Q000379:methods; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D016364:Reading Frames; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012313:RNA