PPE protein (Rv3873) from DNA segment RD1 of Mycobacterium tuberculosis: strong recognition of both specific T-cell epitopes and epitopes conserved within the PPE family.
Proteins encoded by DNA segment RD1 of Mycobacterium tuberculosis 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 esx-lhp operon in this region. In the present study we characterized a third putative open reading frame in this region, rv3873, which encodes a PPE protein. We found that the rv3873 gene is expressed in M. tuberculosis 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 Mycobacterium bovis 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.
Okkels
Limei Meng
LM
Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen, Denmark. lmo@ssi.dk
Brock
Inger
I
Follmann
Frank
F
Agger
Else Marie
EM
Arend
Sandra M
SM
Ottenhoff
Tom H M
TH
Oftung
Fredrik
F
Rosenkrands
Ida
I
Andersen
Peter
P
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D016366:Open Reading Frames; D010446:Peptide Fragments / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology; D014611:Vaccination
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D007371:Interferon-gamma