PMID: 8962126Dec 10, 1996Paper

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

Proceedings of the National Academy of Sciences of the United States of America
Z Grossman, A Singer

Abstract

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 tune 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...Continue Reading

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Citations

Oct 21, 1999·Journal of Cellular Physiology·L Miele, B Osborne
Nov 15, 2002·International Journal of Hematology·Richard K BurtAlberto M Marmont
May 12, 2004·Journal of Theoretical Biology·Hugo A van den Berg, David A Rand
Aug 21, 2003·Journal of Theoretical Biology·Hugo A van den Berg, David A Rand
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Oct 26, 2001·Current Opinion in Immunology·Z Grossman, W E Paul
Mar 26, 2008·Immunology and Cell Biology·Jonathan SprentCharles D Surh
Nov 3, 2010·Immunology and Cell Biology·Gerald WirnsbergerLudger Klein
Jul 9, 2011·Nature Immunology·Jonathan Sprent, Charles D Surh
Jun 28, 2011·Nature Reviews. Immunology·Paul E Love, Avinash Bhandoola
Jan 20, 1999·The Journal of Experimental Medicine·R ZhaoE J Collins
Jan 4, 2001·The Journal of Experimental Medicine·S M AndertonD C Wraith
May 23, 2001·The Journal of Experimental Medicine·P WongA Y Rudensky
Aug 22, 2001·The Journal of Experimental Medicine·P KrajL Ignatowicz
Nov 6, 2002·The Journal of Experimental Medicine·Markus MunderVijay K Kuchroo
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Oct 27, 2005·Journal of Biochemistry and Molecular Biology·Heekyoung ChungRho H Seong
Jul 27, 2000·Seminars in Immunology·Z Grossman, W E Paul

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