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2016 ; 13
(114
): 20150911
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On the organization of human T-cell receptor loci: log-periodic distribution of
T-cell receptor gene segments
#MMPMID26763333
Toor AA
; Toor AA
; Rahmani M
; Manjili MH
J R Soc Interface
2016[Jan]; 13
(114
): 20150911
PMID26763333
show ga
The human T-cell repertoire is complex and is generated by the rearrangement of
variable (V), diversity (D) and joining (J) segments on the T-cell receptor (TCR)
loci. The T-cell repertoire demonstrates self-similarity in terms clonal
frequencies when defined by V, D and J gene segment usage; therefore to determine
whether the structural ordering of these gene segments on the TCR loci
contributes to the observed clonal frequencies, the TCR loci were examined for
self-similarity and periodicity in terms of gene segment organization.
Logarithmic transformation of numeric sequence order demonstrated that the V and
J gene segments for both T-cell receptor ? (TRA) and ? (TRB) loci are arranged in
a self-similar manner when the spacing between the adjacent segments was
considered as a function of the size of the neighbouring gene segment, with an
average fractal dimension of approximately 1.5. Accounting for the gene segments
occurring on helical DNA molecules with a logarithmic distribution, sine and
cosine functions of the log-transformed angular coordinates of the start and stop
nucleotides of successive TCR gene segments showed an ordered progression from
the 5' to the 3' end of the locus, supporting a log-periodic organization. T-cell
clonal frequency estimates, based on V and J segment usage, from normal stem cell
donors were plotted against the V and J segment on TRB locus and demonstrated a
periodic distribution. We hypothesize that this quasi-periodic variation in
gene-segment representation in the T-cell clonal repertoire may be influenced by
the location of the gene segments on the periodic-logarithmically scaled TCR
loci. Interactions between the two strands of DNA in the double helix may
influence the probability of gene segment usage by means of either constructive
or destructive interference resulting from the superposition of the two helices.