title: Design of a polyepitope construct for the induction of HLA-A0201-restricted HIV 1-specific CTL responses using HLA-A*0201 transgenic, H-2 class I KO mice.
abstract: HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin double-knockout mice were used to compare and optimize the immunogenic potential of 17HIV 1-derived,HLA-A0201-restricted epitopic peptides. A tyrosine substitution in position 1 of the epitopic peptides, which increases both their affinity for and their HLA-A0201 molecule stabilizing capacity, was introduced in a significant proportion, having verified that such modifications enhance their immunogenicity in respect of their natural antigenicity. Based on these results, a 13-polyepitope construct was inserted in the pre-S2 segment of the hepatitis B middle glycoprotein and used for DNA immunization. Long-lasting CTL responses against most of the inserted epitopes could be elicited simultaneously in a single animal with cross-recognition in several cases of their most common natural variants.
authors.affiliation: Unité d'Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, Institut Pasteur, Paris, France. firat@genethon.fr
authors.forename: H
authors.initials: H
authors.lastname: Firat
authors.forename: S
authors.initials: S
authors.lastname: Tourdot
authors.forename: A
authors.initials: A
authors.lastname: Ureta-Vidal
authors.forename: A
authors.initials: A
authors.lastname: Scardino
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
authors.forename: F
authors.initials: F
authors.lastname: Buseyne
authors.forename: Y
authors.initials: Y
authors.lastname: Rivìere
authors.forename: O
authors.initials: O
authors.lastname: Danos
authors.forename: M L
authors.initials: ML
authors.lastname: Michel
authors.forename: K
authors.initials: K
authors.lastname: Kosmatopoulos
authors.forename: F A
authors.initials: FA
authors.lastname: Lemonnier
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000939:Epitopes; D006183:H-2 Antigens / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000502:physiology*; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014443:Tyrosine; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D006183:H-2 Antigens; D015234:HLA-A Antigens; D064532:Histocompatibility Antigen H-2D; D019444:Vaccines, DNA; D014443:Tyrosine