title: Differential evolution and stability of epitope-specific CD8(+) T cell responses in EBV infection.
abstract: Murine models of lymphocytic choriomeningitis virus infection suggest that the memory CD8(+) T cell repertoire is reflective of the CD8(+) T cell repertoire generated during acute infection. Less is known regarding the evolution of CD8(+) T cell repertoires during human viral infections. We therefore examined epitope-specific CD8(+) T cell responses in a large cohort of individuals with acute through latent Epstein-Barr virus infection. Using 16 of 20 published EBV epitopes restricted by HLA-A2, HLA-A3 or HLA-B7, we showed that lytic cycle-specific CD8(+) T cell responses predominated during acute EBV infection. However, whereas HLA-A2(+)-restricted BMLF-1-specific CD8(+) T cell responses were maintained through latency, HLA-A2(+)- and HLA-B7(+)-restricted BZLF-1, as well as HLA-A3(+)-restricted BRLF-1 CD8(+) T cell responses, were generated but not readily maintained. Analyses of CD8(+) T cell responses to EBV latent cycle Ags showed delayed detection and lower frequencies of latent epitope-specific CD8(+) T cell responses during acute EBV infection, with maintenance of these responses 1 yr post-EBV infection. Early BMLF-1 and EBNA-3A epitope-specific CD8(+) T cell frequencies did not correlate with their frequencies at 1 yr postinfection. Interestingly, populations of EBV-specific CD8(+) T cells were stable during 20 mo in our long term EBV-seropositive populations, suggesting homeostasis between virus and the host immune system. This study demonstrates that CD8(+) T cell repertoires generated during persistent viral infections are not simply reflective of the initial pool of CD8(+) T cells and provides evidence that the generation of CD8(+) T cell responses to a persistent infection is a dynamic process.
authors.affiliation: Department of Pediatrics and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Catalina
authors.forename: J L
authors.initials: JL
authors.lastname: Sullivan
authors.forename: K R
authors.initials: KR
authors.lastname: Bak
authors.forename: K
authors.initials: K
authors.lastname: Luzuriaga
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D000939:Epitopes; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D009842:Oligopeptides / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D017735:Virus Latency
chemical_list: D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D009842:Oligopeptides; D014764:Viral Proteins