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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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Overlap and effective size of the human CD8+ T cell receptor repertoire

Harlan S Robins1, Santosh K Srivastava, Paulo V Campregher

  • 1Program in Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. hrobins@fhcrc.org

Science Translational Medicine
|September 3, 2010
PubMed

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.

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