THE MIXOTOPE - A COMBINATORIAL PEPTIDE LIBRARY AS A T-CELL AND B-CELLIMMUNOGEN

We report a new approach in peptide vaccine strategy based on combinat orial synthesis. A library of 7.5 x 10(5) related peptides, termed mix otope, 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 an d outbred rodents tested. The response directed against the mixotope i ncluded antibodies, CD4(+) T helper cells (TH1 and TH2) and CD8(+) T c ells. In rodents immunized with the mixotope, the T cell response dire cted against individual V3 peptide sequences (BRU, MN, RF, SF2, and EL I) as measured by T cell proliferation and interleukin (IL)-2 producti on, was found to be major histocompatibility complex haplotype-depende nt. However, additional experiments performed in mice indicated that s electivity 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 e pitopes 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 d esign of future vaccine strategies.