Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand.
We demonstrate that cognate peptide ligands altered at T cell receptor (TCR) contact residues and bound to class II major histocompatability complex can change the cytokine pattern of mature T cell clones. Myelin basic protein peptide 85-99-reactive Th0 T cell clones were stimulated with altered peptide ligands, which acted both as TCR antagonist and induced new mRNA synthesis and protein secretion of TGF-beta 1, while no longer inducing mRNA synthesis or protein secretion of IL-2, IL-4, IL-10, and IFN gamma. The modified peptides failed to induce a detectable calcium flux, p56lck activation, or thymidine incorporation, yet triggered nearly equal amounts of IL-4 secretion in the presence of ionomycin. Antigen-induced modulation of T cell cytokine secretion may be important in regulating the immune response.
Windhagen
A
A
Laboratory of Molecular Immunology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Scholz
C
C
Höllsberg
P
P
Fukaura
H
H
Sette
A
A
Hafler
D A
DA
D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D017931:DNA Primers; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D006680:HLA Antigens; D004676:Myelin Basic Protein; D012333:RNA, Messenger