Enhancement of antigen-specific IFN-gamma production from CD8(+) T cells by a single amino acid-substituted peptide derived from bovine alphas1-casein.
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 alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile 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 stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-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-gamma, a potent inhibitor of Th2-dependent events, including IgE production.
Totsuka
M
M
Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Tokyo, Bunkyo-ku, 113-8657, Japan.
Kakehi
M
M
Kohyama
M
M
Hachimura
S
S
Hisatsune
T
T
Kaminogawa
S
S
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D002364:Caseins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid; D013268:Stimulation, Chemical
D002364:Caseins; D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D009842:Oligopeptides; D010446:Peptide Fragments; C114674:alpha-casein (142-149); D007371:Interferon-gamma