Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designated PE and PE_PGRS. The major difference between these two families is the presence of a domain containing numerous
Gly-Ala repeats extending to the C terminus of the PE_PGRS genes. We have used a representative PE_PGRS gene from M.
tuberculosis, Rv1818c (1818PE_PGRS), and its amino-terminal PE region (1818PE), to investigate the immunological response to these
proteins during experimental
tuberculosis and following immunization with
DNA constructs. During
infection of mice with M.
tuberculosis, a significant humoral immune response was observed against recombinant 1818PE_PGRS but not toward the 1818PE
protein. Similarly, immunization with a 1818PE_PGRS
DNA construct induced
antibodies directed against 1818PE_PGRS but not against 1818PE
proteins, and no humoral response was induced by 1818PE
DNA. These results suggest that certain PE_PGRS genes are expressed during
infection of the host with M.
tuberculosis and that an antibody response is directed solely against the
Gly-Ala-rich PGRS domain. Conversely, splenocytes from 1818PE-vaccinated mice but not mice immunized with 1818PE_PGRS secreted
gamma interferon following in vitro restimulation and demonstrated protection in the mouse
tuberculosis challenge model. These results suggest that the PE
vaccine can elicit an effective cellular immune response and that immune recognition of the PE
antigen is influenced by the
Gly-Ala-rich PGRS domain.