title: Fractal organization of the human T cell repertoire in health and after stem cell transplantation.
abstract: 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.
authors: Bone Marrow Transplant Program, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors: Jeremy
authors: J
authors: Meier
authors: Catherine
authors: C
authors: Roberts
authors: Kassi
authors: K
authors: Avent
authors: Allison
authors: A
authors: Hazlett
authors: Jennifer
authors: J
authors: Berrie
authors: Kyle
authors: K
authors: Payne
authors: David
authors: D
authors: Hamm
authors: Cindy
authors: C
authors: Desmarais
authors: Catherine
authors: C
authors: Sanders
authors: Kevin T
authors: KT
authors: Hogan
authors: Kellie J
authors: KJ
authors: Archer
authors: Masoud H
authors: MH
authors: Manjili
authors: Amir A
authors: AA
authors: Toor
mesh_terms: D000961:Antilymphocyte Serum / Q000494:pharmacology / Q000627:therapeutic use; D002999:Clone Cells; D017709:Fractals; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D019653:Myeloablative Agonists / Q000494:pharmacology / Q000627:therapeutic use; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D016693:Receptors, Antigen, T-Cell, alpha-beta