Numerical Modelling Of The V-J Combinations Of The T Cell Receptor TRA/TRD Locus

Abstract : Lymphocytes of the immune system ensure the body defense by the expression of receptors which are specific of targets, termed antigens. Each lymphocyte, deriving from the same original clone, expresses the same unique receptor. To achieve the production of receptors covering the wide variety of antigens, lymphocytes use a specialized genetic mechanism consisting of gene rearrangements. For instance, the genes encoding the receptor of the alpha chain of the T lymphocyte receptor (TRA) spread over a 1500 Kb genetic region which includes around 100 V genes, 60 J genes, and a single C gene. To constitute a functional alpha chain, one of the V and one of the J genes rearrange together to form a single exon. The precise definition of these V-J combinations is essential to understand the repertoire of TRA. We have developed a numerical model simulating all of the V-J combinations of TRA, fitting the available experimental observations obtained from the analysis of TRA in T lymphocytes of the thymus and the blood. Our model gives new insights on the rules controlling the use of V and J genes in providing a dynamic estimation of the total V-J combinations.