Enhancement of Antigen-Specific IFN-γ Production from CD8+T Cells by a Single Amino Acid-Substituted Peptide Derived from Bovine αs1-Casein

Abstract

Modulation of CD8⁺T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8⁺T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142–149 (p142-149; LAYFYPEL) of α_s1-casein, a major milk allergen, which is a dominant determinant restricted by H-2K^b. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-γ secretion than p142-149 from specific CD8⁺T cells. Furthermore, L142I could prime CD8⁺T cells more efficientlyin vivo,and these L142I-primed cells secreted more IFN-γ than p142-149-primed CD8⁺T cells upon stimulation with p142-149in vitro.These findings are mainly explained by the greater ability of L142I to form stable K^b–peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8⁺T cells which recognize the parent peptide and secrete IFN-γ, a potent inhibitor of Th2-dependent events, including IgE production.