Synthesis of lipopeptides of the immunodominant epitope hMBP(83–99) containing amide or C-C bond linked hydrophobic chains for the study of T cell response
- 31 Downloads
We previously demonstrated that the lipopeptide of the myelin basic protein (MBP) immunodominant epitope in Lewis rat Palm-GpMBP(74-85) (Gp: guinea pig), which induced experimental autoimmune encephalomyelitisin vivo strongly increased the T cell proliferative responsein vitro. We extended this study to the human immunodominant epitope hMBP(83-99), synthesizing different lipophilic peptides bearing a hydrophobic chain linked through an amide or a C-C bond. To this aim, we developed a synthetic pathway for (±)-N-Fmoc-Ahd-OH (Ahd: 2-aminohexadecanoic acid) which was used to synthesize diastereomeric peptides which were successfully separated by reverse-phase high-performance liquid chromatography. MBP-specific T cell lines recognizing the immunodominant epitope hMBP(83-99) have been generated from patients affected by multiple sclerosis. Their proliferative response to the native peptide and to some lipoderivatives has been investigated. In contrast to the animal model, none of the investigated lipopeptides exhibited ‘superagonist’ activity.
Key words2-aminohexadecanoic acid hMBP lipidic α-amino acid lipopeptides T cell response
central nervous system
count per minute
experimental autoimmune encephalomyelitis
electrospray ionization mass spectrometry
fast-atom-bombardment mass spectrometry
flash column chromatography
guinea pig MBP
high-performance liquid chromatography
myelin basic protein
major histocompatibility complex
peripheral blood lymphocytes
solid-phase peptide synthesis
T cell line
T cell receptor
thin layer chromatography
Unable to display preview. Download preview PDF.
- 3.Papini, A.M., Mazzucco, S., Pinzani, D., Biondi, M., Chelli, M., Ginanneschi, M., Rapi, G., Mazzanti, B., Vergelli, M., Massacesi, L., and Amaducci, L., In Tam, J.P. and Kaumaya, P.T.P. (Eds), Peptides: Chemistry, Structure and Biology (Proceedings of the 15th American Peptide Symposium), Kluwer Academic Publishers, Dordrecht, 1998, pp. 700–702.Google Scholar
- 4. a.
- 4. b.
- 4. c.
- 8.Papini, A.M., Mazzucco, S., Nardi, E., Chelli, M., Ginanneschi, M. and Rapi, G., In Tam, J.P. and Kaumaya P.T.P. (Eds.), Peptides: Chemistry, Structure and Biology (Proceedings of the 15th American Peptide Symposium), Kluwer Academic Publishers, Dordrecht, 1998, pp. 345–346.Google Scholar
- 9.Perrin, D.D. and Armarego, W.L.F., In Purification of Laboratory Chemicals, 3rd ed., Pergamon, Oxford, 1988, p. 145.Google Scholar
- 10.Gibbons, W.A., Hughes, R.A., Charalambous, M., Christodoulou, M., Szeto, A., Aulabaugh, A.E., Mascagni, P. and Toth, I., Liebigs Ann. Chem., (1990) 1175.Google Scholar