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The gene for a T lymphocyte triggering factor from African trypanosomes.

Vaidya T, Bakhiet M, Hill KL, Olsson T, Kristensson K, Donelson JE - J. Exp. Med. (1997)

Bottom Line: Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma.Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes.TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242, USA.

ABSTRACT
An early and essential event in the protective immune response against most viruses and protozoa is the production of interferon-gamma (IFN-gamma). In contrast, during infection with African trypanosomes, protozoan parasites that cause human sleeping sickness, the increased levels of IFN-gamma do not correlate with a protective response. We showed previously that African trypanosomes express a protein called T lymphocyte triggering factor (TLTF), which triggers CD8(+) T lymphocytes to proliferate and to secrete IFN-gamma. Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma. Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes. TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

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Predicted amino  acid sequence of TLTF and  comparison to a mouse growth  arrest–specific protein. The trypanosome cDNA sequence predicts a hydrophilic, 453-amino  acid protein of 54 kD. In the  alignment with the mouse protein (GenBank accession No.  U19589) similar amino acid residues, including conservative substitutions, are outlined and positions of identity are shaded. The  two proteins exhibit 59% amino  acid similarity and 35% identity. The deduced protein encoded by a human expressed sequence tag (dbEST accession No. W21172) is nearly identical  (87%) to the mouse protein and also displays 34% identity with TLTF (data not shown). The trypanosome TLTF sequence data are available from  EMBL/GenBank/DDBJ under accession number AF012853.
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Figure 1: Predicted amino acid sequence of TLTF and comparison to a mouse growth arrest–specific protein. The trypanosome cDNA sequence predicts a hydrophilic, 453-amino acid protein of 54 kD. In the alignment with the mouse protein (GenBank accession No. U19589) similar amino acid residues, including conservative substitutions, are outlined and positions of identity are shaded. The two proteins exhibit 59% amino acid similarity and 35% identity. The deduced protein encoded by a human expressed sequence tag (dbEST accession No. W21172) is nearly identical (87%) to the mouse protein and also displays 34% identity with TLTF (data not shown). The trypanosome TLTF sequence data are available from EMBL/GenBank/DDBJ under accession number AF012853.

Mentions: A monoclonal antibody, called MO1, was used to affinity purify TLTF from bloodstream trypanosome extracts. Monovalent polyspecific antiserum directed against the affinity-purified protein was generated in rabbits and used to immunoscreen a cDNA expression library of total RNA isolated from bloodstream forms of T. b. rhodesiense, a subspecies that causes the human disease (6). A cDNA clone was identified that remained immunopositive through multiple rounds of screening. The nucleotide sequence of this cDNA revealed that it was a partial length clone lacking the 39 nucleotide sequence of the 5′ spliced leader, a universal feature of trypanosome mRNAs. A full-length coding sequence was obtained from the product of a reverse transcriptase-PCR amplification of total trypanosome RNA using an internal 3′ primer derived from the TLTF partial cDNA sequence and a 5′ primer matching the 5′ spliced leader sequence. Fig. 1 shows the deduced 453-amino acid sequence of the encoded protein, a 54-kD hydrophilic polypeptide.


The gene for a T lymphocyte triggering factor from African trypanosomes.

Vaidya T, Bakhiet M, Hill KL, Olsson T, Kristensson K, Donelson JE - J. Exp. Med. (1997)

Predicted amino  acid sequence of TLTF and  comparison to a mouse growth  arrest–specific protein. The trypanosome cDNA sequence predicts a hydrophilic, 453-amino  acid protein of 54 kD. In the  alignment with the mouse protein (GenBank accession No.  U19589) similar amino acid residues, including conservative substitutions, are outlined and positions of identity are shaded. The  two proteins exhibit 59% amino  acid similarity and 35% identity. The deduced protein encoded by a human expressed sequence tag (dbEST accession No. W21172) is nearly identical  (87%) to the mouse protein and also displays 34% identity with TLTF (data not shown). The trypanosome TLTF sequence data are available from  EMBL/GenBank/DDBJ under accession number AF012853.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199003&req=5

Figure 1: Predicted amino acid sequence of TLTF and comparison to a mouse growth arrest–specific protein. The trypanosome cDNA sequence predicts a hydrophilic, 453-amino acid protein of 54 kD. In the alignment with the mouse protein (GenBank accession No. U19589) similar amino acid residues, including conservative substitutions, are outlined and positions of identity are shaded. The two proteins exhibit 59% amino acid similarity and 35% identity. The deduced protein encoded by a human expressed sequence tag (dbEST accession No. W21172) is nearly identical (87%) to the mouse protein and also displays 34% identity with TLTF (data not shown). The trypanosome TLTF sequence data are available from EMBL/GenBank/DDBJ under accession number AF012853.
Mentions: A monoclonal antibody, called MO1, was used to affinity purify TLTF from bloodstream trypanosome extracts. Monovalent polyspecific antiserum directed against the affinity-purified protein was generated in rabbits and used to immunoscreen a cDNA expression library of total RNA isolated from bloodstream forms of T. b. rhodesiense, a subspecies that causes the human disease (6). A cDNA clone was identified that remained immunopositive through multiple rounds of screening. The nucleotide sequence of this cDNA revealed that it was a partial length clone lacking the 39 nucleotide sequence of the 5′ spliced leader, a universal feature of trypanosome mRNAs. A full-length coding sequence was obtained from the product of a reverse transcriptase-PCR amplification of total trypanosome RNA using an internal 3′ primer derived from the TLTF partial cDNA sequence and a 5′ primer matching the 5′ spliced leader sequence. Fig. 1 shows the deduced 453-amino acid sequence of the encoded protein, a 54-kD hydrophilic polypeptide.

Bottom Line: Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma.Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes.TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Iowa, and the Howard Hughes Medical Institute, Iowa City, Iowa 52242, USA.

ABSTRACT
An early and essential event in the protective immune response against most viruses and protozoa is the production of interferon-gamma (IFN-gamma). In contrast, during infection with African trypanosomes, protozoan parasites that cause human sleeping sickness, the increased levels of IFN-gamma do not correlate with a protective response. We showed previously that African trypanosomes express a protein called T lymphocyte triggering factor (TLTF), which triggers CD8(+) T lymphocytes to proliferate and to secrete IFN-gamma. Here, we isolate the gene for TLTF and demonstrate that the recombinant version of TLTF specifically induces CD8(+), but not CD4(+), T cells to secrete IFN-gamma. Studies with TLTF fused to the green fluorescent protein show that TLTF is localized to small vesicles that are found primarily at or near the flagellar pocket, the site of secretion in trypanosomes. TLTF is likely to be only the first example of a class of proteins that we designate as trypanokines, i.e., factors secreted by trypanosomes that modulate the cytokine network of the host immune system for the benefit of the parasite.

Show MeSH
Related in: MedlinePlus