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.
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.
Firat
H
H
Unité d'Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, Institut Pasteur, Paris, France. firat@genethon.fr
Tourdot
S
S
Ureta-Vidal
A
A
Scardino
A
A
Suhrbier
A
A
Buseyne
F
F
Rivìere
Y
Y
Danos
O
O
Michel
M L
ML
Kosmatopoulos
K
K
Lemonnier
F A
FA
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
D016915:AIDS Vaccines; D000939:Epitopes; D006183:H-2 Antigens; D015234:HLA-A Antigens; D064532:Histocompatibility Antigen H-2D; D019444:Vaccines, DNA; D014443:Tyrosine