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 lipopeptides obtained by conjugating a palmitoyl moiety at the N(alpha)-terminal of Gln(74) or at the epsilon-NH(2) 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 response, demonstrating that the superagonist inducing effect of lipoconjugation is epitope-specific. Digestion of the two native peptides with cathepsin D and L, both implicated in antigen processing, and with a complete lysosomal fraction of a EBV-transformed B cell line shows that GpMBP(74-85) is resistant to cellular proteases, while GpMBP(82-98) is easily digested by these enzymes. These results suggest that the first prerequisite for increasing the T-cell response by lipoconjugation is the stability of the native peptide to peptidases, providing an important insight into the understanding of the immunoadjuvant effect of lipoderivative antigens.

Palmitoyl Derivatives of GpMBP Epitopes: T-Cell Response and Peptidases Susceptibility / PAPINI A.M.; MAZZANTI B.; NARDI E.; TRAGGIAI E.; BALLERINI C.; BIAGIOLI T.; KALBACHER H.; BECH H.; DEEG M.; CHELLI M.; GINANNESCHI M.; MASSACESI L.; VERGELLI M.;. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 44:(2001), pp. 3504-3510. [10.1021/jm010913j]

Palmitoyl Derivatives of GpMBP Epitopes: T-Cell Response and Peptidases Susceptibility.

PAPINI, ANNA MARIA;BALLERINI, CLARA;GINANNESCHI M.;MASSACESI, LUCA;
2001

Abstract

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 lipopeptides obtained by conjugating a palmitoyl moiety at the N(alpha)-terminal of Gln(74) or at the epsilon-NH(2) 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 response, demonstrating that the superagonist inducing effect of lipoconjugation is epitope-specific. Digestion of the two native peptides with cathepsin D and L, both implicated in antigen processing, and with a complete lysosomal fraction of a EBV-transformed B cell line shows that GpMBP(74-85) is resistant to cellular proteases, while GpMBP(82-98) is easily digested by these enzymes. These results suggest that the first prerequisite for increasing the T-cell response by lipoconjugation is the stability of the native peptide to peptidases, providing an important insight into the understanding of the immunoadjuvant effect of lipoderivative antigens.
2001
44
3504
3510
PAPINI A.M.; MAZZANTI B.; NARDI E.; TRAGGIAI E.; BALLERINI C.; BIAGIOLI T.; KALBACHER H.; BECH H.; DEEG M.; CHELLI M.; GINANNESCHI M.; MASSACESI L.; VERGELLI M.;
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/216865
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