Comparative immune response to PE and PE_PGRS antigens of Mycobacterium tuberculosis

Sequencing of the entire genome of Mycobacterium tuberculosis identified a novel multigene family composed of two closely related subfamilies designat ed PE and PE PGRS. The major difference between these two families is the p resence 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 f rom M. tuberculosis, Rv1818c (1818(PE_PGRS)), and its amino-terminal PE reg ion (1818(PE)), to investigate the immunological response to these proteins during experimental tuberculosis and following immunization with DNA const ructs. During infection of mice with M. tuberculosis, a significant Immoral immune response was observed against recombinant 1818(PE_PGRS) but not tow ard the 1818PE protein. Similarly, immunization with a 1818(PE_PGRS) DNA co nstruct induced antibodies directed against 1818(PE_PGRS) but not against 1 818PE proteins, and no humoral response was induced by 1818(PE) DNA. These results suggest that certain PE_PGRS genes are expressed during infection o f the host with M. tuberculosis and that an antibody response is directed s olely against the Gly-Ala-rich PGRS domain. Conversely, splenocytes from 18 18(PE)-vaccinated mice but not mice immunized with 1818(PE_PGRS) secreted g amma interferon following in vitro restimulation and demonstrated protectio n in the mouse tuberculosis challenge model. These results suggest that the PE vaccine can elicit an effective cellular immune response and that immun e recognition of the PE antigen is influenced by the Gly-Ala-rich PGRS doma in.