A signal integration model for thymic selection
During development, T cells express randomly generated T cell receptors that could potentially recognize any peptide, including self and foreign peptides. In order to select a functional and self-tolerant T cell repertoire, pre-mature T cells undergo a series of selection steps in the thymus, where various self-antigens are presented. We proposed an agent-based model of thymic selection that relies on signal integration of T cells from various interactions with antigen presenting cells. The success of the model in explaining how regulatory and conventional T cells are selected relies on taking into account the history of T cell receptor stimulations. In particular, we could understand with the model why regulatory T cells are more cross-reactive than conventional T cells. Subsequently, the model was used for predictions of how the selected repertoires are changed by manipulations in the thymus. The results help in better understanding tolerance induction and autoimmunity in peripheral T cell repertoires and may suggest strategies of inducing or breaking immune tolerance.
Khailaie S, Robert PA, Toker A, Huehn J, Meyer-Hermann M. A signal integration model of thymic selection and natural regulatory T cell commitment. J Immunol 193 (2014) 5983-96
Sahamoddin Khailaie, Phillipe A. Robert, Alexey Uvarovskii (since 2016 in Heidelberg)
- Systems Immunology- Prof. Dr. Michael Meyer-Hermann