Inhibition of EBV-induced lymphoproliferation by CD4(+) T cells specific for an MHC class II promiscuous epitope.
Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients.
Omiya
Ryusuke
R
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Buteau
Chantal
C
Kobayashi
Hiroya
H
Paya
Carlos V
CV
Celis
Esteban
E
D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D016377:Organ Transplantation / Q000009:adverse effects; D014764:Viral Proteins; D014765:Viral Vaccines / Q000276:immunology
D000956:Antigens, Viral; C402641:EBNA-2 protein, Human herpesvirus 4; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D000949:Histocompatibility Antigens Class II; D014764:Viral Proteins; D014765:Viral Vaccines