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 β 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 Vβ-Jβ pair utilization, dominated by sequences containing few inserted nucleotides, and drawn from a defined subset comprising less than 0.1% of the estimated 5 × 1011 possible sequences. Surprisingly, the overlap in the naïve CD8+ CDR3 sequence repertoires of any two of the individuals is ~7000-fold larger than predicted and appears to be independent of the degree of human leukocyte antigen matching.