Identification of new cytotoxic T-cell epitopes on the 38-kilodalton lipoglycoprotein of Mycobacterium 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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (SciVal)

Abstract

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 histocompatibility 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 lipopeptides up-regulated and stabilized the H-2Db molecules on RMA-S cells. Both lipopeptides, in combination with incomplete Freund's adjuvant, induced CTL responses in C57BL/6 (H-2(b)) 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
Volume66
Issue number7
DOIs
Publication statusPublished - 01 Jul 1998

Keywords

  • Animals
  • Epitopes, T-Lymphocyte
  • Female
  • Glycoproteins/immunology
  • H-2 Antigens/biosynthesis
  • Histocompatibility Antigen H-2D
  • Lipoproteins/immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Weight
  • Mycobacterium tuberculosis/immunology
  • T-Lymphocytes, Cytotoxic/immunology
  • Tumor Cells, Cultured

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