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Numerical Modelling Of The V-J Combinations Of The T Cell Receptor TRA/TRD Locus.
- Source :
- PLoS Computational Biology; Feb2010, Vol. 6 Issue 2, p1-12, 12p, 1 Diagram, 5 Charts, 9 Graphs
- Publication Year :
- 2010
-
Abstract
- T-Cell antigen Receptor (TR) repertoire is generated through rearrangements of V and J genes encoding a and b chains. The quantification and frequency for every V-J combination during ontogeny and development of the immune system remain to be precisely established. We have addressed this issue by building a model able to account for Vα-Jα gene rearrangements during thymus development of mice. So we developed a numerical model on the whole TRA/TRD locus, based on experimental data, to estimate how Va and Ja genes become accessible to rearrangements. The progressive opening of the locus to V-J gene recombinations is modeled through windows of accessibility of different sizes and with different speeds of progression. Furthermore, the possibility of successive secondary V-J rearrangements was included in the modelling. The model points out some unbalanced V-J associations resulting from a preferential access to gene rearrangements and from a non-uniform partition of the accessibility of the J genes, depending on their location in the locus. The model shows that 3 to 4 successive rearrangements are sufficient to explain the use of all the V and J genes of the locus. Finally, the model provides information on both the kinetics of rearrangements and frequencies of each V-J associations. The model accounts for the essential features of the observed rearrangements on the TRA/TRD locus and may provide a reference for the repertoire of the V-J combinatorial diversity. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cell receptors
LYMPHOCYTES
ANTIGENS
GENES
GENETIC recombination
CELL death
Subjects
Details
- Language :
- English
- ISSN :
- 1553734X
- Volume :
- 6
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- PLoS Computational Biology
- Publication Type :
- Academic Journal
- Accession number :
- 48735191
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1000682