|
Conference publicationsAbstractsXXV conferenceEvaluation of the role of T-cell receptor self-organizationMoscow institute of physics and technology, Russia, 141700, Dologprudny, Institutskiy per., 9, +7(903)224-77-33, ivan.prikhodko@phystech.ed 1National medical research center for Hematology Russian Ministry of Health, Russia, 125167, Moscow, Noviy Zykovskiy proezd, 4
The human immune system consists of two subsystems responsible for the recognition of pathogens by characteristic markers and adaptive selection of T-lymphocytes and antibodies specifically interacting with the pathogens identified by the first subsystem [1]. Selection of T-lymphocytes occurs as a result of interaction with short fragments of peptides (epitopes). According to existing data, a small fraction of epitopes which have a greater affinity for T-lymphocyte activates them [2]. Mechanisms of T-lymphocyte recognition of such epitopes are actively studied. The problem is of urgent relevance in connection with the fact that the experiment shows a markedly greater sensitivity and specificity than predicted by the currently available models [3]. We believe that this difference is explained by the latter not taking into account the spatio-temporal correlation of the different epitopes interactions with the T-lymphocyte. This correlation is observed in vitro: contact of the T-lymphocyte with the antigen leads to reversible clustering of T-lymphocyte receptors [4]. As the cluster grows, the probability of fixing new epitopes on it grows, and, consequently, the probability of its decay must fall rapidly. Our analysis allowed us to find an asymptotic expression for the probability of formation of a percolating cluster upon contact of the T-lymphocyte and the antigen presenting cell: $$P_a=1-\prod_i(1-e^{-\lambda_i})$$где, $$\lambda_i = (1+\delta_i) \alpha_i / \theta$$ θ is the dimensionless cluster growth rate parameter, αi and δi are the dimensionless parameters of the association and dissociation rate of the T cell receptor with epitopes in the region of each cluster growth point. Apparently, the percolation probability is small while all λi are large, but even one contact in the region with a epitope fluctuation anomaly of epitopes with small λi can increase the percolation probability to 50%.
Literature 1. Medzhitov R., Preston-Hurlburt P., Janeway Jr C. A. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity //Nature. vol 388, no 6640, Pp 394, 1997. 2. Aleksic M. et al. Dependence of T cell antigen recognition on T cell receptor-peptide MHC confinement time //Immunity. vol 32, no 2, Pp 163-174, 2010 3. Lever M. et al. Phenotypic models of T cell activation //Nature reviews. Immunology. vol 14, no 9, Pp 916, 2014 4. Boyle S. et al. Quantum dot fluorescence characterizes the nanoscale organization of T cell receptors for antigen //Biophysical journal. vol 11, no 11, Pp L57-L59, 2011
|
