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PPE Protein (Rv3873) from DNA Segment RD1 ofMycobacterium tuberculosis: Strong Recognition of Both Specific T-Cell Epitopes and Epitopes Conserved within the PPE Family
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| Zeitschriftentitel: | Infection and Immunity |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | Infection and Immunity, 71, 2003, 11, S. 6116-6123 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>ABSTRACT</jats:title><jats:p>Proteins encoded by DNA segment RD1 of<jats:italic>Mycobacterium tuberculosis</jats:italic>have recently been demonstrated to play important roles in bacterial virulence, vaccine development, and diagnostic reagent design. Previously, we characterized two immunodominant T-cell antigens, the early secreted antigen target (ESAT-6) and the 10-kDa culture filtrate protein (CFP10), which are encoded by the<jats:italic>esx-lhp</jats:italic>operon in this region. In the present study we characterized a third putative open reading frame in this region,<jats:italic>rv3873</jats:italic>, which encodes a PPE protein. We found that the<jats:italic>rv3873</jats:italic>gene is expressed in<jats:italic>M. tuberculosis</jats:italic>H37Rv and that the native protein, Rv3873, is predominantly associated with the mycobacterial cell or wall. When tested as a His-tagged recombinant protein, Rv3873 stimulated high levels of gamma interferon secretion in peripheral blood mononuclear cells isolated from tuberculosis (TB) patients, as well as from healthy tuberculin purified protein derivative-positive donors. In contrast to other RD1-encoded antigens, Rv3873 was also found to be recognized by a significant proportion of<jats:italic>Mycobacterium bovis</jats:italic>BCG-vaccinated donors. Epitope mapping performed with overlapping peptides revealed a broad pattern of T-cell recognition comprising both TB-specific epitopes and epitopes also recognized by BCG-vaccinated donors. The immunodominant epitope (residues 118 to 135) for both TB patients and BCG-vaccinated individuals was found to be highly conserved among a large number of PPE family members.</jats:p> |
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| Umfang: | 6116-6123 |
| ISSN: |
0019-9567
1098-5522 |
| DOI: | 10.1128/iai.71.11.6116-6123.2003 |