SUBSTITUTION OF PEPTIDE-BOND 53-54 OF HEL(52-61) WITH AN ETHYLENE BOND RATHER THAN REDUCED PEPTIDE-BOND IS TOLERATED BY AN MHC-II RESTRICTED T-CELL

To probe the interactions between major histocompatibility class-II mo lecules and the amide bonds of the antigenic peptide main chain, we sy nthesized ethylenic and reduced analogues of HEL(52-61), an immunogeni c peptide for murine major histocompatibility class-II IA(k) restricte d T-cell clones. The synthesis of the corresponding ethylenic analogue of HEL(52-61) in position 53-54 was performed by coupling the Fmoc-pr otected tripeptide Asp-Tyr-Psi[E, CH=CH]Gly with HEL(55-61). Biologica l tests showed that the ethylenic peptide was presented by major histo compatibility class-II IA(k) molecule and recognized by HEL(52-61)-spe cific T-cell clones. The corresponding reduced peptide of HEL(52-61) a t position 53-54 neither stimulated T-cell clones nor competed with th e natural peptide. These results show that, while reduced pseudopeptid es might not be appropriate ethylenic pseudopeptides may be used as pr obes to dissect the role of hydrogen bonding between the peptide main chain and MHC residues and also help in the design of more stable immu nogenic peptides.