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# Computer Modeling of Clonal Dominance: Memory-Anti-Naïve and Its Curbing by Attrition

Castiglione, Filippo; Ghersi, Dario; Celada, Franco

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{
"inLanguage": {
"alternateName": "eng",
"@type": "Language",
"name": "English"
},
"description": "<p>Experimental and computational studies have revealed that T-cell cross-reactivity is a&nbsp;widespread phenomenon that can either be advantageous or detrimental to the host.&nbsp;In particular, detrimental effects can occur whenever the clonal dominance of memory&nbsp;cells is not justified by their infection-clearing capacity. Using an agent-based model&nbsp;of the immune system, we recently predicted the &ldquo;memory anti-na&iuml;ve&rdquo; phenomenon,&nbsp;which occurs when the secondary challenge is similar but not identical to the primary&nbsp;stimulation. In this case, the pre-existingmemory cells formed during the primary infection&nbsp;may be rapidly deployed in spite of their low affinity and can actually prevent a potentially&nbsp;higher affinity na&iuml;ve response from emerging, resulting in impaired viral clearance. This&nbsp;finding allowed us to propose a mechanistic explanation for the concept of &ldquo;antigenic&nbsp;sin&rdquo; originally described in the context of the humoral response. However, the fact&nbsp;that antigenic sin is a relatively rare occurrence suggests the existence of evolutionary&nbsp;mechanisms that can mitigate the effect of the memory anti-na&iuml;ve phenomenon. In&nbsp;this study we use computer modeling to further elucidate clonal dominance and the&nbsp;memory anti-na&iuml;ve phenomenon, and to investigate a possible mitigating factor called&nbsp;attrition. Attrition has been described in the experimental and computational literature&nbsp;as a combination of competition for space and apoptosis of lymphocytes via type-I&nbsp;interferon in the early stages of a viral infection. This study systematically explores&nbsp;the relationship between clonal dominance and the mechanism of attrition. Our results&nbsp;suggest that attrition can indeed mitigate the memory anti-na&iuml;ve effect by enabling the&nbsp;emergence of a diverse, higher affinity na&iuml;ve response against the secondary challenge.<br>\nIn conclusion, modeling attrition allows us to shed light on the nature of clonal interaction&nbsp;and dominance.&nbsp;</p>",
"creator": [
{
"affiliation": "National Research Council of Italy",
"@type": "Person",
"name": "Castiglione, Filippo"
},
{
"affiliation": "College of Information Science and Technology, University of Nebraska",
"@type": "Person",
"name": "Ghersi, Dario"
},
{
"affiliation": "NYU School of Medicine, New York",
"@type": "Person",
}
],
"headline": "Computer Modeling of Clonal Dominance: Memory-Anti-Na\u00efve and Its Curbing by Attrition",
"datePublished": "2019-07-26",
"url": "https://zenodo.org/record/3351968",
"keywords": [
"computer modeling",
"IMMSIM",
"memory-anti-naive",
"attrition",
"CD8+ response"
],
"@context": "https://schema.org/",
"identifier": "https://doi.org/10.3389/fimmu.2019.01513",
"@id": "https://doi.org/10.3389/fimmu.2019.01513",
"@type": "ScholarlyArticle",
"name": "Computer Modeling of Clonal Dominance: Memory-Anti-Na\u00efve and Its Curbing by Attrition"
}
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