July 26, 2019 Journal article Open Access

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>", 
  "license": "https://creativecommons.org/licenses/by/4.0/legalcode", 
  "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", 
      "name": "Celada, Franco"
    }
  ], 
  "headline": "Computer Modeling of Clonal Dominance: Memory-Anti-Na\u00efve and Its Curbing by Attrition", 
  "image": "https://zenodo.org/static/img/logos/zenodo-gradient-round.svg", 
  "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"
}