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.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Moran
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Cameron
authors.initials: C
authors.lastname: Simmons
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Nguyen Vinh
authors.initials: NV
authors.lastname: Chau
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Luhn
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Phuong Dung
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Le Thi Thu
authors.initials: LTT
authors.lastname: Thao
authors.affiliation: Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.affiliation: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005416:Flavivirus / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D018984:Epitopes, T-Lymphocyte