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

Sz. Bősze, Nadia Caccamo, Zs. Majer, G. Mező, Francesco Dieli, F. Hudecz

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15 Citations (Scopus)

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 91SEFAYGSFVRTVSL104 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 91Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N-terminal of residue 92Glu produced a shorter peptide (Ac- 92EFAYGSFVRTVSL104) exhibiting properties required for efficient T-cell responses. CD measurements indicated that peptide 91SEFAYGSFVRTVSLPVGADE110 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.

Original languageEnglish
Pages (from-to)467-476
Number of pages10
JournalBiopolymers - Peptide Science Section
Volume76
Issue number6
DOIs
Publication statusPublished - 2004

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Oligopeptides
T-cells
Mycobacterium tuberculosis
Peptides
Proteins
T-Lymphocytes
Immunodominant Epitopes
Mycobacterium Infections
Subunit Vaccines
T-Lymphocyte Epitopes
Epitopes
Tuberculin
Vaccines
In Vitro Techniques
Blood Cells
Clone Cells
Conformations
Elongation
Blood
Lead

Keywords

  • 16-kDa protein of Mycobacterium tuberculosis
  • Identification of T-cell epitope
  • Mycobacterium tuberculosis specific protein antigen
  • Peptide epitopes
  • Specificity of CD4 T-cell clones and peripheral blood mononuclear cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

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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 91SEFAYGSFVRTVSL104 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 91Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N-terminal of residue 92Glu produced a shorter peptide (Ac- 92EFAYGSFVRTVSL104) exhibiting properties required for efficient T-cell responses. CD measurements indicated that peptide 91SEFAYGSFVRTVSLPVGADE110 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.",
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T1 - In vitro T-cell immunogenicity of oligopeptides derived from the region 92-110 of the 16-kDa protein of mycobacterium tuberculosis

AU - Bősze, Sz.

AU - Caccamo, Nadia

AU - Majer, Zs.

AU - Mező, G.

AU - Dieli, Francesco

AU - Hudecz, F.

PY - 2004

Y1 - 2004

N2 - 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 91SEFAYGSFVRTVSL104 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 91Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N-terminal of residue 92Glu produced a shorter peptide (Ac- 92EFAYGSFVRTVSL104) exhibiting properties required for efficient T-cell responses. CD measurements indicated that peptide 91SEFAYGSFVRTVSLPVGADE110 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.

AB - 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 91SEFAYGSFVRTVSL104 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 91Ser resulted in an almost complete loss of functionality. However, the introduction of an acetyl group at the N-terminal of residue 92Glu produced a shorter peptide (Ac- 92EFAYGSFVRTVSL104) exhibiting properties required for efficient T-cell responses. CD measurements indicated that peptide 91SEFAYGSFVRTVSLPVGADE110 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.

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