In vitro T-cell immunogenicity of oligopeptides derived from the region 92–110 of the 16-kDa protein of Mycobacterium tuberculosis

✍ Scribed by Szilvia Bősze; Nadia Caccamo; Zsuzsa Majer; Gábor Mező; Francesco Dieli; Ferenc Hudecz

• Publisher: Wiley (John Wiley & Sons)
• Year: 2004
• Tongue: English
• Weight: 150 KB
• Volume: 76
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.20153

✦ Synopsis

Abstract

The 16‐kDa protein of Mycobacterium tuberculosis provokes specific immune responses; it is thus a target for the development of peptide‐based diagnostic reagents and subunit vaccines. Previous studies have demonstrated the presence of several regions containing murine and human T‐cell epitopes. Within the 91–110 immunodominant domain, we found that peptides comprising the sequence of ^91^SEFAYGSFVRTVSL^104^ elicit specific T‐cell responses in both human T‐cell clones and human peripheral blood mononuclear cells (PBMC) from PPD^+^ (purified protein derivative) individuals. Elongation of this peptide towards the C‐terminal end did not provide more effective peptides, but the removal of residue ^91^Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N‐terminal of residue ^92^Glu produced a shorter peptide (Ac‐^92^EFAYGSFVRTVSL^104^) exhibiting properties required for efficient T‐cell responses. CD measurements indicated that peptide ^91^SEFAYGSFVRTVSLPVGADE^110^ adopts a helical conformation in triflouroethanol. We found that the N‐terminal part of this sequence plays a major role in the induction of proliferative T‐cell responses and is responsible for the highly ordered, helical secondary structure. The “lead” structure described here could also be considered in the development of synthetic peptides or multicomponent peptide mixtures for the early detection, monitoring, or preventing Mycobacterium tuberculosis infection with optimized T‐cell response‐provoking capacity. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004