Single amino acid substitutions on a Japanese cedar pollen allergen (Cry j 1)-derived peptide induced alterations in human T cell responses and T cell receptor antagonism.
We generated T cell clones specific to a Japanese cedar pollen allergen (Cry j 1) and investigated effects of altered T cell receptor (TCR) ligand on changes of T cell responses. One of these Cry j 1-specific T cell clones established from patients with Japanese cedar pollinosis, ST1.9, recognized an antigenic peptide Cry j 1 p335-346 in the context of HLA-DRA+DRB3*0301 molecules and secreted interleukin-4 dominantly, with a smaller amount of interferon-gamma. ST1.9 represented one of the major T cell clones specific to Cry j 1 in the donor, because a short-term cultured polyclonal T cell line specific to Cry j 1 exhibited the same character as the ST1.9. We synthesized various analog peptides derived from Cry j 1 p335-346 with single amino acid substitutions and determined key residues for interactions between TCR of ST1.9 and HLA-DR molecules. We also analyzed changes in the responses of ST1.9 to Cry j 1 p335-346-derived analog peptides. Of interest was that the substitution of 339threonine to valine resulted in a significant increase in interferon-gamma production, with no remarkable changes either in proliferative response or interleukin-4 production. Analog peptides carrying the substitutions of 339threonine to glycine or glutamine revealed TCR antagonism, without changes in their binding affinities to the DR molecule. Therefore single amino acid substitutions on an allergen peptide carrying the T cell epitope may suppress helper-T-dependent class switch pressure to IgE in B cells either by inducing increased interferon-gamma production or by inhibiting proliferative responses in helper-T cells.
Ikagawa
S
S
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Matsushita
S
S
Chen
Y Z
YZ
Ishikawa
T
T
Nishimura
Y
Y
D000485:Allergens; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D017951:Antigen Presentation; D052179:Antigens, Plant; D002455:Cell Division; D002999:Clone Cells; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology*; D011058:Pollen / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000485:Allergens; D000596:Amino Acids; D052179:Antigens, Plant; C065290:Cry j I protein, Cryptomeria japonica; D006684:HLA-DR Antigens; D007376:Interleukin-2; D010455:Peptides; D010940:Plant Proteins; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma