The mixotope: a combinatorial peptide library as a T cell and B cell immunogen.
We report a new approach in peptide vaccine strategy based on combinatorial synthesis. A library of 7.5 x 10(5) related peptides, termed mixotope, was derived from the sequence of the third hypervariable domain (V3 loop) of the human immunodeficiency virus (HIV) envelope protein. This preparation induced a strong immune response in all syngeneic and outbred rodents tested. The response directed against the mixotope included antibodies, CD4+ T helper cells (TH1 and TH2) and CD8+ T cells. In rodents immunized with the mixotope, the T cell response directed against individual V3 peptide sequences (BRU, MN, RF, SF2, and ELI) as measured by T cell proliferation and interleukin (IL)-2 production, was found to be major histocompatibility complex haplotype-dependent. However, additional experiments performed in mice indicated that selectivity was less restrictive when using IL-3 secretion to explore T cell activation. This combinatorial antigen could be considered as a series of agretopic motifs framing a multiplicity of closely related epitopes for T cell recognition and able to elicit a T cell and B cell repertoire. This new construct may therefore provide a basis for the design of future vaccine strategies.
Estaquier
J
J
Unité mixte INSERM U167-CNRS 624, Lille, France.
Gras-Masse
H
H
Boutillon
C
C
Ameisen
J C
JC
Capron
A
A
Tartar
A
A
Auriault
C
C
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D007376:Interleukin-2; D011498:Protein Precursors; D014614:Vaccines, Synthetic