منابع مشابه
A mathematical analysis of TCR serial triggering and down-regulation.
Despite the increasing knowledge on the pathways involved in TCR signal transduction and T cell activation, the molecular mechanism of TCR triggering by ligand, MHC-peptide complexes, is still elusive and controversial. The present paper addresses the controversy on the early events of TCR engagement and triggering. Mathematical modelling techniques are applied to experimental data to infer pla...
متن کاملMathematical modeling of chimeric TCR triggering predicts the magnitude of target lysis and its impairment by TCR downmodulation.
We investigated relationships among chimeric TCR (cTCR) expression density, target Ag density, and cTCR triggering to predict lysis of target cells by cTCR(+) CD8(+) T human cells as a function of Ag density. Triggering of cTCR and canonical TCR by Ag could be quantified by the same mathematical equation, but cTCR represented a special case in which serial triggering was abrogated. The magnitud...
متن کاملLck, Membrane Microdomains, and TCR Triggering Machinery: Defining the New Rules of Engagement
In spite of a comprehensive understanding of the schematics of T cell receptor (TCR) signaling, the mechanisms regulating compartmentalization of signaling molecules, their transient interactions, and rearrangement of membrane structures initiated upon TCR engagement remain an outstanding problem. These gaps in our knowledge are exemplified by recent data demonstrating that TCR triggering is la...
متن کاملThe Serial Engagement Model 17 Years After: From TCR Triggering to Immunotherapy
More than 15 years ago the serial engagement model was proposed as an attempt to solve the low affinity/high sensitivity paradox of TCR antigen recognition. Since then, the model has undergone ups and downs marked by the technical and conceptual advancements made in the field of T lymphocyte activation. Here, I describe the development of the model and survey recent literature providing evidenc...
متن کاملTriggering the TCR Developmental Checkpoint Activates a Therapeutically Targetable Tumor Suppressive Pathway in T-cell Leukemia.
UNLABELLED Cancer onset and progression involves the accumulation of multiple oncogenic hits, which are thought to dominate or bypass the physiologic regulatory mechanisms in tissue development and homeostasis. We demonstrate in T-cell acute lymphoblastic leukemia (T-ALL) that, irrespective of the complex oncogenic abnormalities underlying tumor progression, experimentally induced, persistent T...
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ژورنال
عنوان ژورنال: Immunity
سال: 2001
ISSN: 1074-7613
DOI: 10.1016/s1074-7613(01)00155-8