Epstein-Barr nuclear antigen 1-specific CD4(+) Th1 cells kill Burkitt's lymphoma cells.
The gamma-herpesvirus, EBV, is reliably found in a latent state in endemic Burkitt's lymphoma. A single EBV gene product, Epstein-Barr nuclear Ag 1 (EBNA1), is expressed at the protein level. Several mechanisms prevent immune recognition of these tumor cells, including a block in EBNA1 presentation to CD8(+) killer T cells. Therefore, no EBV-specific immune response has yet been found to target Burkitt's lymphoma. We now find that EBNA1-specific, Th1 CD4(+) cytotoxic T cells recognize Burkitt's lymphoma lines. CD4(+) T cell epitopes of EBNA1 are predominantly found in the C-terminal, episome-binding domain of EBNA1, and approximately 0.5% of peripheral blood CD4(+) T cells are specific for EBNA1. Therefore, adaptive immunity can be directed against Burkitt's lymphoma, and perhaps this role for CD4(+) Th1 cells extends to other tumors that escape MHC class I presentation.
Paludan
Casper
C
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
Bickham
Kara
K
Nikiforow
Sarah
S
Tsang
Ming L
ML
Goodman
Kiera
K
Hanekom
Willem A
WA
Fonteneau
Jean-Francois
JF
Stevanović
Stefan
S
Münz
Christian
C
D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000276:immunology*; D053222:Fas Ligand Protein; D006683:HLA-DQ Antigens / Q000502:physiology; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D018417:Th1 Cells / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D019014:fas Receptor; C417029:EBV-encoded nuclear antigen 1