Palmitoyl derivatives of GpMBP epitopes: T-cell response and peptidases susceptibility

We report for the first time the immunoadjuvant effects of lipoconjugation of peptide antigens in an in vitro system by using CD4+ T-cells. The lipope ptides obtained by conjugating a palmitoyl moiety at the N-alpha-terminal o f Gln74 or at the epsilon -NH2 of Lys(75) of GpMBP(74-85) induced increased T-cell responsiveness compared to the native nonlipidated peptide. On the other hand, lipoderivatives of GpMBP(82-98) did not increase the T-cell res ponse, demonstrating that the superagonist inducing effect of lipoconjugati on is epitope-specific. Digestion of the two native peptides with cathepsin D and L, both implicated in antigen processing, and with a complete lysoso mal fraction of a EBV-transformed B cell line shows that GpMBP(74-85) is re sistant to cellular proteases, while GpMBP(82-98) is easily digested by the se enzymes. These results suggest that the first prerequisite for increasin g the T-cell response by lipoconjugation is the stability of the native pep tide to peptidases, providing an important insight into the understanding o f the immunoadjuvant effect of lipoderivative antigens.