The growth threshold conjecture: a theoretical framework for understanding T-cell tolerance
Adaptive immune responses depend on the capacity of T cells to target specific antigens. As similar antigens can be expressed by pathogens and host cells, the question naturally arises of how can T cells discriminate friends from foes. In this work, we suggest that T cells tolerate cells whose proli...
| Autores: | , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Recursos: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/23565 |
| Acesso em linha: | https://hdl.handle.net/20.500.14352/23565 |
| Access Level: | acceso abierto |
| Palavra-chave: | 577.27 51:57 T cells Immune tolerance Negative selection Immunodominance Immune self Inmunología Biología molecular (Biología) Biomatemáticas 2412 Inmunología 2415 Biología Molecular 2404 Biomatemáticas |
| Resumo: | Adaptive immune responses depend on the capacity of T cells to target specific antigens. As similar antigens can be expressed by pathogens and host cells, the question naturally arises of how can T cells discriminate friends from foes. In this work, we suggest that T cells tolerate cells whose proliferation rates remain below a permitted threshold. Our proposal relies on well-established facts about T-cell dynamics during acute infections: T-cell populations are elastic (they expand and contract) and they display inertia (contraction is delayed relative to antigen removal). By modelling inertia and elasticity, we show that tolerance to slow-growing populations can emerge as a population-scale feature of T cells. This result suggests a theoretical framework to understand immune tolerance that goes beyond the self versus non-self dichotomy. It also accounts for currently unexplained observations, such as the paradoxical tolerance to slow-growing pathogens or the presence of self-reactive T cells in the organism. |
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