Rescue of the immunotherapeutic potential of a novel T cell epitope in the Epstein-Barr virus latent membrane protein 2.
Epstein-Barr virus (EBV)-associated tumors express a limited number of viral antigens but most of them express the latent membrane protein 2 (LMP2). This article describes a peptide derived from LMP2 (residues 396-404, designated LLL) as a potentially useful vaccine. This peptide could at first be defined as an unlikely T cell target as it could not stabilize MHC surface expression in transporter associated with antigen-processing (TAP)-deficient cells. Nevertheless, T lymphocytes reactive to LLL were detected in the peripheral blood of four EBV-seropositive healthy individuals. We have constructed a chimeric molecule in which LLL was fused to the amino-terminal end of the beta(2) microglobulin (beta(2)m). Autologous dendritic cells constitutively expressing the LLLbeta(2)m molecule were capable of expanding in vitro HLA-A2-restricted anti-LLL T lymphocytes from the peripheral blood of one of the donors. These T lymphocytes exhibited cytolytic activity against target cells expressing the chimeric molecules as well as against EBV-infected lymphoblastoid cells expressing natural LLL-MHC complexes.
Lalonde
Annick
A
Laval University Cancer Research Center, McMahon St 9, Quebec City, QC, Canada G1R 2J6.
Avila-Cariño
Javier
J
Caruso
Manuel
M
de Campos-Lima
Pedro O
PO
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000276:immunology / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010455:Peptides; D014763:Viral Matrix Proteins; D001613:beta 2-Microglobulin