Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4(+) T cells

Cancer Res. 2002 Dec 15;62(24):7195-9.


The EBV-encoded nuclear antigen 1 (EBNA1) is required for the maintenance and replication of the viral episome in EBV-transformed human B-lymphoblastoid cell lines. It is expressed in all EBV-associated tumors, making it a potentially important target for immunotherapy. However, this promise has not been realized, because an endogenously processed MHC class I-restricted T-cell epitope remains to be identified, and relatively little is known about MHC class II-restricted helper epitopes in the molecule. In this report, we identify a T-cell peptide derived from EBNA1 that is recognized by CD4(+) T cells. More importantly, EBNA1-specific, HLA-DP3-restricted CD4(+) T cells are capable of recognizing MHC class II-matched Burkitt's lymphoma cells, autologous peripheral blood mononuclear cells loaded with the purified EBNA1 protein, as well as target cells transfected with Ii-EBNA1 cDNA. These new findings demonstrate that EBNA1 is processed endogenously and presented to T cells by MHC class II molecules, and, hence, may be useful to incorporate into cancer vaccines to enhance antitumor immunity against EBV-associated tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigen Presentation
  • Burkitt Lymphoma / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Clone Cells
  • Epitopes, T-Lymphocyte / immunology*
  • Epstein-Barr Virus Nuclear Antigens / genetics
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • HLA-DP Antigens / genetics
  • HLA-DP Antigens / immunology*
  • HLA-DP beta-Chains
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured


  • Epitopes, T-Lymphocyte
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-DP Antigens
  • HLA-DP beta-Chains
  • HLA-DPw3 antigen
  • Peptide Fragments
  • EBV-encoded nuclear antigen 1