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 ∼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.