A repetitive sequence of Epstein-Barr virus nuclear antigen 6 comprises overlapping T cell epitopes which induce HLA-DR-restricted CD4+ T lymphocytes

E. Rajnavolgyi, Noémi Nagy, Britt Thuresson, Z. Dosztányi, A. Simon, I. Simon, Robert W. Karr, Ingemar Ernberg, Eva Klein, Kerstin I. Falk

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Most human adults carry the Epstein-Barr virus (EBV) and develop immunological memory against the structural and the virus-encoded cellular proteins. The EBV nuclear antigen 6 (EBNA6) elicits cytotoxic T cell responses and it also maintains a persistent antibody response. The majority of sera from EBV-seropositive individuals reacts with a synthetic peptide, p63, comprising 21 amino acids of a repetitive region of EBNA6. CD4+ T lymphocytes, with specificity for p63, could be recalled from the T cell repertoire of EBV carriers that expressed certain HLA-DR allotypes which were identified as good binders of p63 by an in vitro flow cytometric assay. Analysis of the HLA-DR/p63 interaction by molecular mechanics calculations indicated the presence of multiple overlapping epitopes which were predicted to bind in a HLA-DRB1 allo- and subtype-specific manner. Specific activation of p63-selected long-term CD4+ T cell cultures resulted in a proliferative response, in the production of IL-2 and in the secretion of high levels of tumor necrosis factor as measured by bioassays. Proliferation and cytokine production of p63-specific T cells could be induced by p63-loaded HLA-DR-matched antigen-presenting cells and by B cells co-expressing relevant HLA-DR molecules and EBNA6. Our results show that peptides of an EBNA6 repeat region induce CD4+ T cells which can react with EBNA6-carrying cells in many individuals. We suggest that these T(h) cells may be important in conditioning dendritic cells for initiation potent virus-specific immune responses, provide help for EBV-specific B cells, drive IgG isotype switch and support the sustained effector function of memory cytotoxic T lymphocytes.

Original languageEnglish
Pages (from-to)281-293
Number of pages13
JournalInternational Immunology
Volume12
Issue number3
Publication statusPublished - 2000

Fingerprint

Epstein-Barr Virus Nuclear Antigens
T-Lymphocyte Epitopes
Nucleic Acid Repetitive Sequences
HLA-DR Antigens
Human Herpesvirus 4
T-Lymphocytes
B-Lymphocytes
Immunologic Memory
Viruses
HLA-DRB1 Chains
Peptides
Cytotoxic T-Lymphocytes
Antigen-Presenting Cells
Mechanics
Biological Assay
Dendritic Cells
Antibody Formation
Interleukin-2
Epitopes
Cell Culture Techniques

Keywords

  • HLA-DR-peptide interaction
  • Human CD4 T lymphocyte
  • Virus-specific immunity

ASJC Scopus subject areas

  • Immunology

Cite this

A repetitive sequence of Epstein-Barr virus nuclear antigen 6 comprises overlapping T cell epitopes which induce HLA-DR-restricted CD4+ T lymphocytes. / Rajnavolgyi, E.; Nagy, Noémi; Thuresson, Britt; Dosztányi, Z.; Simon, A.; Simon, I.; Karr, Robert W.; Ernberg, Ingemar; Klein, Eva; Falk, Kerstin I.

In: International Immunology, Vol. 12, No. 3, 2000, p. 281-293.

Research output: Contribution to journalArticle

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AU - Dosztányi, Z.

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