Minimum peptide sequences necessary for priming and triggering of humoral and cell-mediated immune responses in mice: use of synthetic peptide antigens of defined structure.

Abstract

The smallest peptide sequences required to induce humoral and cell-mediated immune responses in mice were determined by using the following synthetic peptide and polypeptide antigens of defined amino acid sequence: TNP-(Glu-Tyr-Lys) (TNP-3), TNP-(Glu-Tyr-Lys-Glu-Tyr-Ala), (TNP-6), TNP-[Glu-Tyr-Lys-(Glu-Tyr-Ala)2] (TNP-9), TNP-[Glu-Tyr-Lys-(Glu-Tyr-Ala)3] (TNP-12), TNP-[Glu-Tyr-Lys-(Glu-Tyr-Ala)5] (TNP-18), TNP-Poly [Glu-Tyr-Lys-(Glu-Tyr-Ala)5] (TNP-Poly-18), and Poly (Glu-Tyr-Ala) (Poly GTA). Peptides containing three and six amino acid residues (TNP-3 and TNP-6) were nonimmunogenic. Antigen with nine amino acid residues (TNP-9) could prime the responder mice for antibody and T cell proliferative responses but not for the delayed hypersensitivity (DTH) responses. The peptide containing 12 amino acid residues (TNP-12) could prime for the antibody, T cell proliferative, as well as for the DTH responses. To elicit these responses, peptides larger than the minimum priming sequences were required. Eighteen amino acid peptide TNP-18, and its sequential polymer TNP-Poly-18, will prime as well as elicit all of these responses. Antisera raised against TNP-12, TNP-18, and TNP-Poly-18 were directed towards the stable α-helical determinants of these antigens. We also conclude that the same immune response (Ir) genes in the mouse histocompatibility complex control the expression of T cell proliferation, DTH, and the antibody responses.