Identification of new cytotoxic T-cell epitopes on the 38-Kilodalton lipoglycoprotein of Mycobacteriurn tuberculosis by using lipopeptides

Dora P.A.J. Da Fonseca, Dianne Joosten, Ruurd Van Der Zee, Danny L. Jue, Mahavir Singh, Hans M. Vordermeier, Harm Snippe, André F.M. Verheul

Research output: Contribution to journalArticlepeer-review


Induction of cytotoxic T lymphocytes (CTLs) by vaccination has been shown to protect against bacterial, viral, and tumoral challenge. The aim of this study was to identify CTL epitopes on the 38-kDa lipoglycoprotein from Mycobacterium tuberculosis. The identification of these CTL epitopes was based on synthesizing peptides designed from the 38-kDa lipoglycoprotein, with known major his tocompatibility complex class I (MHC-I) binding motifs (H-2Db), and studying their ability to up-regulate and stabilize MHC-I molecules on the mouse lymphoma cell line RMA-S. To improve the capacity of the identified peptides to induce CTL responses in mice, palmitic acid with a cysteine-serine-serine spacer amino acid sequence was attached to the amino terminus of the peptide. Two of five peptides with H-2Db binding motifs and their corresponding iipopeptides up-regulated and stabilized the H-2D(b) molecules on RMA-S cells. Both lipopeptides, in combination with incomplete Freund's adjuvant, induced CTL responses in C57BL/6 (H-2b) mice. Moreover, the lipopeptide induced stronger CTL responses than the peptide. The capacity of the various lipopeptides to induce CTL displayed a good relationship with the ability of the (lipo)peptide to up-regulate and to stabilize H-2Db molecules. The capacity of the peptides and lipopeptides to up-regulate and stabilize MHC-I expression can therefore be used to predict their potential to function as a CTL epitope. The newly identified CTL epitopes and their lipid derivatives provide us with important information for future M. tuberculosis vaccine design.

Original languageEnglish
Pages (from-to)3190-3197
Number of pages8
JournalInfection and Immunity
Issue number7
Publication statusPublished - 01 Jul 1998


Dive into the research topics of 'Identification of new cytotoxic T-cell epitopes on the 38-Kilodalton lipoglycoprotein of Mycobacteriurn tuberculosis by using lipopeptides'. Together they form a unique fingerprint.

Cite this