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.
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.
Moran
Edward
E
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Simmons
Cameron
C
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Chau
Nguyen Vinh
NV
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Luhn
Kerstin
K
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Wills
Bridget
B
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Phuong Dung
Nguyen
N
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Thao
Le Thi Thu
LTT
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Hien
Tran Tinh
TT
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Farrar
Jeremy
J
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Rowland-Jones
Sarah
S
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Dong
Tao
T
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
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
D018984:Epitopes, T-Lymphocyte