Regions of high antigenicity within the hypothetical PPE major polymorphic tandem repeat open-reading frame, Rv2608, show a differential humoral response and a low T cell response in various categories of patients with tuberculosis.
The function of the PE/PPE families of proteins, which represent approximately 10% of the coding capacity of the Mycobacterium tuberculosis genome, has remained relatively unknown. We earlier described a PPE family member, Rv2430c, as an immunodominant antigen. We now report another PPE family gene, Rv2608, a member of the major polymorphic tandem repeat subfamily, for its ability to elicit a high humoral and a low T cell response. Rv2608 was also found to be polymorphic in different clinical isolates of M. tuberculosis, as determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. A total of 51 clinically confirmed patients with tuberculosis (TB), belonging to 3 different categories--fresh infection (n=22), relapsed infection (n=21), and extrapulmonary infection (n=8)--and 10 healthy control subjects were included in the study. Recombinant Rv2608 protein showed positive reactivity to patients' serum samples. Enzyme-linked immunosorbent assays and T cell-proliferation assays with synthetic peptides corresponding to predicted regions of high antigenicity showed a predominantly humoral response in patients with relapsed TB. We additionally identified the Gly-X-Gly-Asn-X-Gly repeat motifs as being primarily responsible for eliciting a humoral immune response.
Chakhaiyar
Prachee
P
Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Nagalakshmi
Yellajosyula
Y
Aruna
Bandi
B
Murthy
Kolluri J R
KJ
Katoch
Vishwa M
VM
Hasnain
Seyed E
SE
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D016366:Open Reading Frames; D013601:T-Lymphocytes / Q000276:immunology*; D020080:Tandem Repeat Sequences; D014376:Tuberculosis / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial