Determination of a HLA II promiscuous peptide cocktail as potential vaccine against EBV latency II malignancies.
The Epstein-Barr virus (EBV) is associated with several malignant diseases, which can be distinguished by their patterns of viral latent gene expression. The latency II program is limited to the expression of the nonimmunodominant antigens EBNA1, LMP1 and LMP2 and is seen in EBV-positive Hodgkin disease, nasopharyngeal carcinomas, and peripheral T/NK-cell lymphomas. CD4 T cells may play a crucial role in controlling these EBV latency II malignancies. In this study, we used the prediction software TEPITOPE to predict promiscuous major histocompatibility complex class II epitopes derived from the latency II antigens EBNA1, LMP1, and LMP2. The predicted peptides were then submitted to peptide-binding assays on HLA II purified molecules, which allowed the selection of 6 peptides (EBNA1: 3; LMP1: 1; and LMP2: 2) with a highly promiscuous capability of binding. This peptide cocktail was immunogenic in a model of HLA-DR1 transgenic mice, leading to a specific cellular and humoral TH1 response. The peptides were also recognized by human CD4 T cells from individuals expressing various HLA II genotypes. This promiscuous peptide cocktail could be immunogenic in the majority of the population and may be used as a peptide-based vaccine in EBV latency II malignancies.
Depil
Stéphane
S
UMR 8527, CNRS, Institut de Biologie, Lille, France. sdepil@nordnet.fr
Moralès
Olivier
O
Castelli
Florence A
FA
Delhem
Nadira
N
François
Violaine
V
Georges
Bertrand
B
Dufossé
Françoise
F
Morschhauser
Franck
F
Hammer
Juergen
J
Maillère
Bernard
B
Auriault
Claude
C
Pancré
Véronique
V
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015798:HLA-DR1 Antigen / Q000235:genetics; D022283:Herpesvirus Vaccines / Q000737:chemistry / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012984:Software; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D015798:HLA-DR1 Antigen; D022283:Herpesvirus Vaccines; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010455:Peptides; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1