Overlap and effective size of the human CD8+ T cell receptor repertoire.
Diversity in T lymphocyte antigen receptors is generated by somatic rearrangement of T cell receptor (TCR) genes and is concentrated within the third complementarity-determining region 3 (CDR3) of each chain of the TCR heterodimer. We sequenced the CDR3 regions from millions of rearranged TCR beta chain genes in naïve and memory CD8(+) T cells of seven adults. The CDR3 sequence repertoire realized in each individual is strongly biased toward specific V(beta)-J(beta) pair utilization, dominated by sequences containing few inserted nucleotides, and drawn from a defined subset comprising less than 0.1% of the estimated 5 x 10(11) possible sequences. Surprisingly, the overlap in the naïve CD8(+) CDR3 sequence repertoires of any two of the individuals is approximately 7000-fold larger than predicted and appears to be independent of the degree of human leukocyte antigen matching.
Robins
Harlan S
HS
Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. hrobins@fhcrc.org
Srivastava
Santosh K
SK
Campregher
Paulo V
PV
Turtle
Cameron J
CJ
Andriesen
Jessica
J
Riddell
Stanley R
SR
Carlson
Christopher S
CS
Warren
Edus H
EH
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics* / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
C067361:CD8 receptor; D022801:Complementarity Determining Regions; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell
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