Identification of HLA-DP3-restricted peptides from EBNA1 recognized by CD4(+) T cells.
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.
Voo
Kui Shin
KS
The Center for Cell and Gene Therapy, Department of Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Fu
Tihui
T
Heslop
Helen E
HE
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
Wang
Rong-Fu
RF
D000483:Alleles; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D002051:Burkitt Lymphoma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology*; D006682:HLA-DP Antigens / Q000235:genetics / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C055961:HLA-DPw3 antigen; D010446:Peptide Fragments; C417029:EBV-encoded nuclear antigen 1