Differential targeting and shifts in the immunodominance of Epstein-Barr virus--specific CD8 and CD4 T cell responses during acute and persistent infection.
The evolution of Epstein-Barr virus (EBV)-specific T cell responses that occurs during the acute and persistent stages of infection remains poorly characterized despite its importance for developing immune interventions for EBV-associated disorders. This study assessed T cell responses to 113 EBV-derived epitopes in 40 subjects with acute or persistent EBV infection. Although no significant differences were seen in the breadth of CD8 and CD4 T cell responses, their magnitude differed significantly over time; acutely infected subjects generated especially strong responses to lytic viral antigens. The cross-sectional shift in immunodominance was also confirmed in subjects followed longitudinally from acute to persistent infection. In addition, human leukocyte antigen-matched siblings with discordant histories of symptomatic EBV infection showed no significant differences in their response patterns, suggesting that symptomatic EBV infection does not lead to unique persistent-stage responses. These data provide an assessment of immunodominance patterns and guidance for developing immunotherapeutic interventions for EBV-associated disorders.
Woodberry
Tonia
T
Partners AIDS Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Suscovich
Todd J
TJ
Henry
Leah M
LM
Davis
Jennifer K
JK
Frahm
Nicole
N
Walker
Bruce D
BD
Scadden
David T
DT
Wang
Frederick
F
Brander
Christian
C
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008969:Molecular Sequence Data
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes