Abstract
| - We report for the first time the immunoadjuvant effects of lipoconjugation of peptide antigensin an in vitro system by using CD4+ T-cells. The lipopeptides obtained by conjugating apalmitoyl moiety at the Nα-terminal of Gln74 or at the ε-NH2 of Lys75 of GpMBP(74−85) inducedincreased T-cell responsiveness compared to the native nonlipidated peptide. On the other hand,lipoderivatives of GpMBP(82−98) did not increase the T-cell response, demonstrating that thesuperagonist inducing effect of lipoconjugation is epitope-specific. Digestion of the two nativepeptides with cathepsin D and L, both implicated in antigen processing, and with a completelysosomal fraction of a EBV-transformed B cell line shows that GpMBP(74−85) is resistant tocellular proteases, while GpMBP(82−98) is easily digested by these enzymes. These resultssuggest that the first prerequisite for increasing the T-cell response by lipoconjugation is thestability of the native peptide to peptidases, providing an important insight into theunderstanding of the immunoadjuvant effect of lipoderivative antigens.
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