Differential evolution and stability of epitope-specific CD8(+) T cell responses in EBV infection

UMMS Affiliation

Department of Pediatrics; Program in Molecular Medicine

Publication Date


Document Type



Acute Disease; Adolescent; Adult; CD8-Positive T-Lymphocytes; Cohort Studies; Epitopes; Epstein-Barr Virus Infections; Epstein-Barr Virus Nuclear Antigens; HLA-A Antigens; HLA-B Antigens; Herpesvirus 4, Human; Humans; Immunologic Memory; Oligopeptides; Viral Proteins; Virus Latency


Life Sciences | Medicine and Health Sciences


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.

DOI of Published Version



J Immunol. 2001 Oct 15;167(8):4450-7.

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

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Link to Article in PubMed

PubMed ID