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 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.
Papini
A M
AM
Dipartimento di Chimica Organica "Ugo Schiff" and Centro di Studio sulla Chimica e la Struttura dei Composti Eterociclici e loro Applicazioni del C.N.R., Polo Scientifico Universitario, Sesto Fiorentino, Italy. annamaria.papini@unifi.it
Mazzanti
B
B
Nardi
E
E
Traggiai
E
E
Ballerini
C
C
Biagioli
T
T
Kalbacher
H
H
Beck
H
H
Deeg
M
M
Chelli
M
M
Ginanneschi
M
M
Massacesi
L
L
Vergelli
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002402:Cathepsin D / Q000737:chemistry; D056668:Cathepsin L; D002403:Cathepsins / Q000737:chemistry; D002455:Cell Division; D003546:Cysteine Endopeptidases; D000939:Epitopes; D005260:Female; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D004676:Myelin Basic Protein / Q000276:immunology*; D019308:Palmitic Acid / Q000737:chemistry*; D010446:Peptide Fragments / Q000276:immunology*; D010447:Peptide Hydrolases / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship
D000939:Epitopes; D008074:Lipoproteins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D019308:Palmitic Acid; D002403:Cathepsins; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534280:Ctsl protein, rat; D002402:Cathepsin D