Cutting edge: Immunoregulation of Th cells by naturally processed peptide antagonists

Th cells recognize protein Ags as short peptides bound to MHC class II mole cules. Altered peptide ligands can antagonize (inhibit) T cell responses to stimulatory peptides. Peptides generated by APC may contain peptide flanki ng 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 t o native protein or the immunogenic epitope delivered by a recombinant infl uenza virus. These data provide the first evidence that Ag processing gener ates both stimulatory and antagonist peptides from a single immunogenic epi tope, an observation that may have important implications for T cell immuno regulation and autoimmunity.