A Monte Carlo Simulation for the Construction of Cytotoxic T Lymphocytes Repertoire

Castiglione, Filippo

doi:10.5772/15456

Cited by 3 publications

(3 citation statements)

References 36 publications

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“…Agent-based simulations have been used to study discrete biological phenomena such as the spread of infectious endemic agents throughout populations (Juher et al, 2009) and the diversification of lymphocyte antigen-receptor repertoires (Castiglione, 2011). The benefit of using this method to model L. monocytogenes cell-to-cell spread is that it allows simulation of individual bacteria as discrete particles and avoids the continuum assumption imposed by Equation 1.…”

Section: Resultsmentioning

confidence: 99%

Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Ortega

Koslover

Theriot

2019

eLife

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Listeria monocytogenes hijacks host actin to promote its intracellular motility and intercellular spread. While L. monocytogenes virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate that L. monocytogenes cell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistent L. monocytogenes infection in an actively extruding epithelium. Thus, our results indicate that L. monocytogenes cell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

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Section: Resultsmentioning

confidence: 99%

Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Ortega

Koslover

Theriot

2019

eLife

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show abstract

“…Agent-based simulations have been used to study discrete biological phenomena such as the spread of infectious endemic agents throughout populations (Juher et al, 2009) and the diversification of lymphocyte antigen-receptor repertoires (Castiglione, 2014). The benefit of using this method to model L. monocytogenes cell-to-cell spread is that it allows simulation of individual bacteria as discrete particles and avoids the continuum assumption imposed by Equation 1.…”

Section: Stochastic Simulations Of Cell-to-cell Spread Via Random Walmentioning

confidence: 99%

Listeria monocytogenescell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Ortega

Koslover

Theriot

2018

Preprint

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L. monocytogenes hijacks host actin to promote its intracellular motility and intercellular spread. While L. monocytogenes virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate that L. monocytogenes cell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistent L. monocytogenes infection in an actively extruding epithelium. Thus, our results indicate that L. monocytogenes cell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia.

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“…String model, which approximates protein-protein interactions as the sum of relevant, ladder-forming AA pair interactions, has been used to study TCR-pMHC interactions [18][19][20][21]. The calculation cost of using a combination of the string model and M-J matrix to estimate TCR-pMHC interactions is quite low, and several attempts have been made to evaluate TCR-pMHC interactions based on this model [22][23][24][25]. Kosmrlj et al applied this method to explain the effect of an MHC molecule on T cell repertoire formation, particularly its capacity to bind diversified peptides, and seem to have succeeded to some extent [26,27].…”

Section: Introductionmentioning

confidence: 99%

Exhaustive Characterization of TCR–pMHC Binding Energy Estimated by the String Model and Miyazawa-Jernigan Matrix

Tsurui

Takahashi²,

Matsuda³

et al. 2014

General Med

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Accurate calculations of protein-protein binding free energies based on rigorous models, which consider the binding complex structure in atomic detail, are computationally expensive and impracticable to apply to T cell repertoire formation that occurs in the thymus because this process involves the interactions among numerous combinations of T cell receptors (TCRs) and presented peptides. By comparison, an evaluation of binding free-energy using a combination of the string model and Miyazawa-Jernigan matrix is very efficient and was therefore applied to estimate interaction energies between T cell receptor-peptide-MHC (TCR-pMHC) complexes, which appeared to successfully explain the effects of binding capacity of MHC on repertoire-formation and the reason for the presence of elite-controllers of some viral infections. However, this evaluation method is overly simplified and requires more detailed considerations when applied to evaluating TCR-pMHC interactions. In this study, we examined this method exhaustively and revealed the limitations of the method. Following features necessitate cautious attitude when interpreting the calculation results: first, the apparent increase in the number of hot spots in accordance with an increase of educational epitope pool size does not mean an increased TCR specificity of surviving clones; second, strong binders to any TCR converge to some limited sequences that are determined by the physical nature of the Miyazawa-Jernigan matrix.

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A Monte Carlo Simulation for the Construction of Cytotoxic T Lymphocytes Repertoire

Cited by 3 publications

References 36 publications

Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Listeria monocytogenes cell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Listeria monocytogenescell-to-cell spread in epithelia is heterogeneous and dominated by rare pioneer bacteria

Exhaustive Characterization of TCR–pMHC Binding Energy Estimated by the String Model and Miyazawa-Jernigan Matrix

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