title: How many TCR clonotypes does a body maintain?
abstract: We consider the lifetime of a T cell clonotype, the set of T cells with the same T cell receptor, from its thymic origin to its extinction in a multiclonal repertoire. Using published estimates of total cell numbers and thymic production rates, we calculate the mean number of cells per TCR clonotype, and the total number of clonotypes, in mice and humans. When there is little peripheral division, as in a mouse, the number of cells per clonotype is small and governed by the number of cells with identical TCR that exit the thymus. In humans, peripheral division is important and a clonotype may survive for decades, during which it expands to comprise many cells. We therefore devise and analyse a computational model of homeostasis of a multiclonal population. Each T cell in the model competes for self pMHC stimuli, cells of any one clonotype only recognising a small fraction of the many subsets of stimuli. A constant mean total number of cells is maintained by a balance between cell division and death, and a stable number of clonotypes by a balance between thymic production of new clonotypes and extinction of existing ones. The number of distinct clonotypes in a human body may be smaller than the total number of naive T cells by only one order of magnitude.
authors.affiliation: Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK. Electronic address: grant@maths.leeds.ac.uk.
authors.forename: Grant
authors.initials: G
authors.lastname: Lythe
authors.affiliation: Institute for Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, Gower Street, London WC1N 1EH, UK.
authors.forename: Robin E
authors.initials: RE
authors.lastname: Callard
authors.affiliation: Institute for Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology, University College London, Gower Street, London WC1N 1EH, UK.
authors.forename: Rollo L
authors.initials: RL
authors.lastname: Hoare
authors.affiliation: Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Carmen
authors.initials: C
authors.lastname: Molina-París
mesh_terms: D000465:Algorithms; D000818:Animals; D002455:Cell Division; D003198:Computer Simulation; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D051379:Mice; D008962:Models, Theoretical; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: Clonal repertoire; Competition; Extinction; Homeostasis; Stochastic modelling; T cells