[HTML][HTML] Fractal organization of the human T cell repertoire in health and after stem cell transplantation

J Meier, C Roberts, K Avent, A Hazlett, J Berrie… - Biology of Blood and …, 2013 - Elsevier
J Meier, C Roberts, K Avent, A Hazlett, J Berrie, K Payne, D Hamm, C Desmarais, C Sanders
Biology of Blood and Marrow Transplantation, 2013Elsevier
T cell repertoire diversity is generated in part by recombination of variable (V), diversity (D),
and joining (J) segments in the T cell receptor β (TCR) locus. T cell clonal frequency
distribution determined by high-throughput sequencing of TCR β in 10 stem cell
transplantation (SCT) donors revealed a fractal, self-similar frequency distribution of unique
TCR bearing clones with respect to V, D, and J segment usage in the T cell repertoire of
these individuals. Further, ranking of T cell clones by frequency of gene segment usage in …
T cell repertoire diversity is generated in part by recombination of variable (V), diversity (D), and joining (J) segments in the T cell receptor β (TCR) locus. T cell clonal frequency distribution determined by high-throughput sequencing of TCR β in 10 stem cell transplantation (SCT) donors revealed a fractal, self-similar frequency distribution of unique TCR bearing clones with respect to V, D, and J segment usage in the T cell repertoire of these individuals. Further, ranking of T cell clones by frequency of gene segment usage in the observed sequences revealed an ordered distribution of dominant clones conforming to a power law, with a fractal dimension of 1.6 and 1.8 in TCR β DJ and VDJ containing clones in healthy stem cell donors. This self-similar distribution was perturbed in the recipients after SCT, with patients demonstrating a lower level of complexity in their TCR repertoire at day 100 followed by a modest improvement by 1 year post-SCT. A large shift was observed in the frequency distribution of the dominant T cell clones compared to the donor, with fewer than one third of the VDJ-containing clones shared in the top 4 ranks. In conclusion, the normal T cell repertoire is highly ordered with a TCR gene segment usage that results in a fractal self-similar motif of pattern repetition across levels of organization. Fractal analysis of high-throughput TCR β sequencing data provides a comprehensive measure of immune reconstitution after SCT.
Elsevier