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Infection and Immunity, September 2001, p. 5606-5611, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5606-5611.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Comparative Immune Response to PE and PE_PGRS Antigens of Mycobacterium tuberculosis

Giovanni Delogudagger and Michael J. Brennan*

Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 24 January 2001/Returned for modification 3 April 2001/Accepted 31 May 2001

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.

* Corresponding author. Mailing address: CBER/FDA, Bldg. 29, Rm. 502, 29 Lincoln Dr. (HFM-431), Bethesda, MD 20892. Phone: (301) 496-9559. Fax: (301) 402-2776. E-mail: Brennan{at}cber.fda.gov.

dagger Present address: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.

Infection and Immunity, September 2001, p. 5606-5611, Vol. 69, No. 9
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.9.5606-5611.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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Copyright © 2001 by the American Society for Microbiology. All rights reserved.