Differential Targeting and Shifts in the Immunodominance of Epstein‐Barr Virus–Specific CD8 and CD4 T Cell Responses during Acute and Persistent Infection

• Published in: The Journal of infectious diseases Vol. 192; no. 9; pp. 1513 - 1524
• Main Authors: Woodberry, Tonia , Suscovich, Todd J. , Henry, Leah M. , Davis, Jennifer K. , Frahm, Nicole , Walker, Bruce D. , Scadden, David T. , Wang, Frederick , Brander, Christian
• Format: Journal Article
• Language: English
• Published: United States The University of Chicago Press 01.11.2005; University of Chicago Press; Oxford University Press
• Subjects: Alleles; Amino Acid Sequence; Antigens; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Epstein Barr virus infections; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - physiology; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; HLA antigens; Human herpesvirus 4; Humans; Immunodominant Epitopes - immunology; Infections; Molecular Sequence Data; Siblings; T lymphocytes; Viruses
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/491741

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.