CTL RECOGNITION OF AN ALTERED PEPTIDE ASSOCIATED WITH ASPARAGINE BONDREARRANGEMENT - IMPLICATIONS FOR IMMUNITY AND VACCINE DESIGN

The extent to which peptides containing chemically and post-translatio nally modified amino acid side chains are recognized by primed CTL has not been clearly defined. We report on the CTL recognition of a MHC c lass I-restricted peptide containing a cyclized asparagine (succinimid e) residue. This modification of the asparagine side chain is a common intermediate structure during deamidation, isomerization, and bond re arrangements of amide-containing amino acids and also occurs as a side reaction in peptide synthesis. The CTL specifically recognized the su ccinimide-containing peptide showing only weak cross-reactivity at hig h concentrations of the parent peptide containing unmodified asparagin e. Similarly, CTL raised against the parent peptide did not recognize the succinimide derivative of this peptide. Naturally processed forms of these structures are likely to occur given the importance and frequ ency of deamidation both in vitro and in vivo. Moreover, since succini mide intermediates of deamidated peptides can occasionally be very sta ble, these peptides have the potential to act as altered self-Ags with significant implications for autoimmunity. In addition, unwanted and potentially hazardous specificities may be elicited when using synthet ic peptides in subunit vaccines in which succinimide residues may form spontaneously during storage or chemical synthesis.