ENHANCEMENT OF ANTIGEN-SPECIFIC IFN-GAMMA PRODUCTION FROM CD8(-CELLS BY A SINGLE AMINO ACID-SUBSTITUTED PEPTIDE DERIVED FROM BOVINE ALPHA(S1)-CASEIN() T)

Modulation of CD8(+) T-cell responses specific for an exogenous antige n by epitope variants would be advantageous to develop a novel means o f;antigen-specific immune regulation. We have analyzed CD8(+) T-cell r esponses to single amino acid-substituted variants of a peptide corres ponding to residues 142-149 (p142-149; LAYFYPEL) of alpha(s1)-casein, a major milk allergen, which is a dominant determinant restricted by H -2K(b). An analog peptide L142I with a substitution of lie for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stim ulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable K-b-peptide complexes. Th ese findings indicate that appropriate analog peptides may be useful a s efficient inducers of CD8(+) T cells which recognize the parent pept ide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production. (C) 1998 Academic Press.