title: Identification of novel immunodominant CD4+ Th1-type T-cell peptide epitopes from herpes simplex virus glycoprotein D that confer protective immunity.
abstract: The molecular characterization of the epitope repertoire on herpes simplex virus (HSV) antigens would greatly expand our knowledge of HSV immunity and improve immune interventions against herpesvirus infections. HSV glycoprotein D (gD) is an immunodominant viral coat protein and is considered an excellent vaccine candidate antigen. By using the TEPITOPE prediction algorithm, we have identified and characterized a total of 12 regions within the HSV type 1 (HSV-1) gD bearing potential CD4(+) T-cell epitopes, each 27 to 34 amino acids in length. Immunogenicity studies of the corresponding medium-sized peptides confirmed all previously known gD epitopes and additionally revealed four new immunodominant regions (gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), each containing naturally processed epitopes. These epitopes elicited potent T-cell responses in mice of diverse major histocompatibility complex backgrounds. Each of the four new immunodominant peptide epitopes generated strong CD4(+) Th1 T cells that were biologically active against HSV-1-infected bone marrow-derived dendritic cells. Importantly, immunization of H-2(d) mice with the four newly identified CD4(+) Th1 peptide epitopes but not with four CD4(+) Th2 peptide epitopes induced a robust protective immunity against lethal ocular HSV-1 challenge. These peptide epitopes may prove to be important components of an effective immunoprophylactic strategy against herpes.
authors.affiliation: Department of Ophthalmology, University of California-Irvine, College of Medicine, Orange, California 92868, USA. Lbenmoha@uci.edu
authors.forename: Lbachir
authors.initials: L
authors.lastname: BenMohamed
authors.forename: Georges
authors.initials: G
authors.lastname: Bertrand
authors.forename: Cory D
authors.initials: CD
authors.lastname: McNamara
authors.forename: Helene
authors.initials: H
authors.lastname: Gras-Masse
authors.forename: Juergen
authors.initials: J
authors.lastname: Hammer
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics*; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology*; D022283:Herpesvirus Vaccines / Q000235:genetics / Q000494:pharmacology; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018417:Th1 Cells / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D022283:Herpesvirus Vaccines; D016056:Immunodominant Epitopes; D007376:Interleukin-2; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D007371:Interferon-gamma