Immunoregulation of Th cells by naturally processed peptide antagonists.
Th cells recognize protein Ags as short peptides bound to MHC class II molecules. Altered peptide ligands can antagonize (inhibit) T cell responses to stimulatory peptides. Peptides generated by APC may contain peptide flanking residues (PFR), which lie outside the minimal binding epitope and can be recognized by the TCR. Our data show that PFR-dependent T cells were found to be potently antagonized by peptides that lack PFR and responded poorly to native protein or the immunogenic epitope delivered by a recombinant influenza virus. These data provide the first evidence that Ag processing generates both stimulatory and antagonist peptides from a single immunogenic epitope, an observation that may have important implications for T cell immunoregulation and autoimmunity.
Carson
R T
RT
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38101, USA.
Desai
D D
DD
Vignali
K M
KM
Vignali
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D002645:Chickens; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D007113:Immunity, Innate; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D010063:Ovum; D010446:Peptide Fragments / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D010766:Phosphorylation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017252:CD3 Complex; D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014443:Tyrosine; D009113:Muramidase