title: Overlap and effective size of the human CD8+ T cell receptor repertoire.
abstract: 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.
authors.affiliation: Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. hrobins@fhcrc.org
authors.forename: Harlan S
authors.initials: HS
authors.lastname: Robins
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: Paulo V
authors.initials: PV
authors.lastname: Campregher
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Turtle
authors.forename: Jessica
authors.initials: J
authors.lastname: Andriesen
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
mesh_terms: 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
chemical_list: C067361:CD8 receptor; D022801:Complementarity Determining Regions; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell
references.citation: Nature. 1988 Aug 4;334(6181):395-402
references.pmid: 3043226
references.citation: Blood. 2009 Nov 5;114(19):4099-107
references.pmid: 19706884
references.citation: J Exp Med. 1994 Dec 1;180(6):2335-40
references.pmid: 7964506
references.citation: Nat Rev Immunol. 2008 Mar;8(3):231-8
references.pmid: 18301425
references.citation: Nature. 1986 Jan 2-8;319(6048):28-33
references.pmid: 3484541
references.citation: J Exp Med. 2001 Nov 5;194(9):1385-90
references.pmid: 11696602
references.citation: Bioinformatics. 2004 Aug 4;20 Suppl 1:i379-85
references.pmid: 15262823
references.citation: Annu Rev Immunol. 2006;24:419-66
references.pmid: 16551255
references.citation: J Immunol. 2008 Dec 1;181(11):7853-62
references.pmid: 19017975
references.citation: Eur J Immunol. 1995 Nov;25(11):3115-22
references.pmid: 7489751