Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone

Edward Moran, Cameron Simmons, Nguyen Vinh Chau, Kerstin Luhn, Bridget Wills, Nguyen Phuong Dung, Le Thi Thu Thao, Tran Tinh Hien, Bridget Wills, Nguyen Phuong Dung, Le Thi Thu Thao, Tran Tinh Hien, Jeremy Farrar, Sarah Rowland-Jones, Tao Dong

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Dengue is a member of the Flaviviridae, a large group of related viruses some of which co-circulate in certain regions (e.g. dengue and Yellow fever in South America). Immune responses cross-reactive between different dengue serotypes are important in the pathogenesis of dengue disease but it is not known whether previous infection with one flavivirus might affect the clinical course of subsequent infections with other members of the family. CD4+ T cells have been shown to be important in the production of cytokines in response to dengue infection and can demonstrate significant epitope cross-reactivity. Here, we describe the generation and characterisation of CD4+ T cell clones from a patient experiencing acute dengue infection. These clones were DRB1*15+ and recognised epitope variants not only within other dengue viruses but certain other flaviviruses. This cross-reactivity was dependent upon the presence of a five-amino acid core region, consistent with structural observations of class II MHC binding to TCR demonstrating that only a subset of residues within an epitope bound to a class II molecule are "read out" by the TCR. This capacity of CD4+ T cell clones to recognise a given epitope despite considerable variation between viruses may be of pathological significance, particularly in regions where related viruses co-circulate.

Original languageEnglish
Pages (from-to)1050-1057
Number of pages8
JournalEuropean Journal of Immunology
Volume38
Issue number4
DOIs
Publication statusPublished - 1 Apr 2008

Keywords

  • Dengue
  • Epitope
  • T cell

Cite this

Moran, Edward ; Simmons, Cameron ; Chau, Nguyen Vinh ; Luhn, Kerstin ; Wills, Bridget ; Dung, Nguyen Phuong ; Thao, Le Thi Thu ; Hien, Tran Tinh ; Wills, Bridget ; Dung, Nguyen Phuong ; Thao, Le Thi Thu ; Hien, Tran Tinh ; Farrar, Jeremy ; Rowland-Jones, Sarah ; Dong, Tao. / Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone. In: European Journal of Immunology. 2008 ; Vol. 38, No. 4. pp. 1050-1057.
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title = "Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone",
abstract = "Dengue is a member of the Flaviviridae, a large group of related viruses some of which co-circulate in certain regions (e.g. dengue and Yellow fever in South America). Immune responses cross-reactive between different dengue serotypes are important in the pathogenesis of dengue disease but it is not known whether previous infection with one flavivirus might affect the clinical course of subsequent infections with other members of the family. CD4+ T cells have been shown to be important in the production of cytokines in response to dengue infection and can demonstrate significant epitope cross-reactivity. Here, we describe the generation and characterisation of CD4+ T cell clones from a patient experiencing acute dengue infection. These clones were DRB1*15+ and recognised epitope variants not only within other dengue viruses but certain other flaviviruses. This cross-reactivity was dependent upon the presence of a five-amino acid core region, consistent with structural observations of class II MHC binding to TCR demonstrating that only a subset of residues within an epitope bound to a class II molecule are {"}read out{"} by the TCR. This capacity of CD4+ T cell clones to recognise a given epitope despite considerable variation between viruses may be of pathological significance, particularly in regions where related viruses co-circulate.",
keywords = "Dengue, Epitope, T cell",
author = "Edward Moran and Cameron Simmons and Chau, {Nguyen Vinh} and Kerstin Luhn and Bridget Wills and Dung, {Nguyen Phuong} and Thao, {Le Thi Thu} and Hien, {Tran Tinh} and Bridget Wills and Dung, {Nguyen Phuong} and Thao, {Le Thi Thu} and Hien, {Tran Tinh} and Jeremy Farrar and Sarah Rowland-Jones and Tao Dong",
year = "2008",
month = "4",
day = "1",
doi = "10.1002/eji.200737699",
language = "English",
volume = "38",
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Moran, E, Simmons, C, Chau, NV, Luhn, K, Wills, B, Dung, NP, Thao, LTT, Hien, TT, Wills, B, Dung, NP, Thao, LTT, Hien, TT, Farrar, J, Rowland-Jones, S & Dong, T 2008, 'Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone' European Journal of Immunology, vol. 38, no. 4, pp. 1050-1057. https://doi.org/10.1002/eji.200737699

Preservation of a critical epitope core region is associated with the high degree of flaviviral cross-reactivity exhibited by a dengue-specific CD4+ T cell clone. / Moran, Edward; Simmons, Cameron; Chau, Nguyen Vinh; Luhn, Kerstin; Wills, Bridget; Dung, Nguyen Phuong; Thao, Le Thi Thu; Hien, Tran Tinh; Wills, Bridget; Dung, Nguyen Phuong; Thao, Le Thi Thu; Hien, Tran Tinh; Farrar, Jeremy; Rowland-Jones, Sarah; Dong, Tao.

In: European Journal of Immunology, Vol. 38, No. 4, 01.04.2008, p. 1050-1057.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Moran, Edward

AU - Simmons, Cameron

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AU - Luhn, Kerstin

AU - Wills, Bridget

AU - Dung, Nguyen Phuong

AU - Thao, Le Thi Thu

AU - Hien, Tran Tinh

AU - Wills, Bridget

AU - Dung, Nguyen Phuong

AU - Thao, Le Thi Thu

AU - Hien, Tran Tinh

AU - Farrar, Jeremy

AU - Rowland-Jones, Sarah

AU - Dong, Tao

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