title: High epitope expression levels increase competition between T cells.
abstract: Both theoretical predictions and experimental findings suggest that T cell populations can compete with each other. There is some debate on whether T cells compete for aspecific stimuli, such as access to the surface on antigen-presenting cells (APCs) or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and, hence, different epitope-specific T cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T cells of different epitope specificity. Understanding mechanisms of T cell coexistence has important practical implications for immune therapies that require a broad immune response.
authors.affiliation: Theoretical Biology, Institute of Integrative Biology, Swiss Federal Institute of Technology, Zurich, Switzerland.
authors.forename: Almut
authors.initials: A
authors.lastname: Scherer
authors.forename: Marcel
authors.initials: M
authors.lastname: Salathé
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bonhoeffer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II