Mathematical analysis of the repertoire of immune cells in healthy donors and autoimmune patients
October 2014
Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia
T lymphocytes are the key drivers of the adaptive immune system and detect, combat, and memorize pathogens in all their possible variations. Specific recognition of potentially harmful foreign peptides is achieved by the highly selective binding of T cell receptors (TCRs) to peptide-MHC complexes (p-MHC), mounted on the surface of specialized antigen-presenting cells. Required diversity of recognition arises due to an astronomic number of distinct molecular variants of TCRs. Still, a T cell typically expresses a single TCR variant, and all its daughter cells have identical antigen recognition properties, constituting a clonotype. The clonal structure of the human peripheral T-cell repertoire is shaped by a number of processes and its accurate tuning leads to a remarkable ability to combat pathogens in all their variety, while systemic failures may lead to severe consequences like autoimmune diseases. In the present study, the researchers developed a statistical approach to assess T cell clonal size distributions from recent next-generation sequencing data from human donors, 41 healthy individuals and one patient with autoimmune disease. The study shows that the clonal structure is globally the same in the healthy individual but different for the autoimmune patient before therapy and converging towards a typical value after therapy. The data shows the importance of theoretical understanding and mathematical modelling of adaptive immunity.
Assessing T cell clonal size distribution: a non-parametric approach
Mikhail V. Ivanchenko
Added on: 10-27-2021
[1] https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108658[2] https://data.jrc.ec.europa.eu/dataset/700397b2-edd7-4ed6-86f7-fc1b164ed432
