Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus

Zvi Grossman*, Alfred Singer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Immature CD4+CD8+ thymocytes expressing T-cell antigen receptors (TCR) are selected by TCR-mediated recognition of peptides associated with major histocompatibility complex molecules on thymic stromal cells. Selection ensures reactivity of the mature cells to foreign antigens and tolerance to self. Although much has been learned about the factors that determine whether a thymocyte with a given specificity will be positively or negatively selected, selection as an aspect of the developmental process as a whole is less well-understood. Here we invoke a model in which thymocytes tone their response characteristics individually and dynamically in the course of development. Cellular development and selection are driven by receptor- mediated metabolic perturbations. Perturbation is a measure of the net intracellular change induced by external stimulation. It results from the integration of several signals and countersignals over time and therefore depends on the environment and the maturation stage of the cell. Individual cell adaptation limits the range of perturbations. Such adaptation renders thymocytes less sensitive to the level of stimulation per se, but responsive to environmental changes in that level. This formulation begins to explain the mechanisms that link developmental and selection events to each other.

Original languageEnglish
Pages (from-to)14747-14752
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number25
StatePublished - 10 Dec 1996


Dive into the research topics of 'Tuning of activation thresholds explains flexibility in the selection and development of T cells in the thymus'. Together they form a unique fingerprint.

Cite this