The co-operonic PE25/PPE41 protein complex of Mycobacterium tuberculosis elicits increased humoral and cell mediated immune response.
BACKGROUND
Many of the PE/PPE proteins are either surface localized or secreted outside and are thought to be a source of antigenic variation in the host. The exact role of these proteins are still elusive. We previously reported that the PPE41 protein induces high B cell response in TB patients. The PE/PPE genes are not randomly distributed in the genome but are organized as operons and the operon containing PE25 and PPE41 genes co-transcribe and their products interact with each other.


RESULTS
We now describe the antigenic properties of the PE25, PPE41 and PE25/PPE41 protein complex coded by a single operon. The PPE41 and PE25/PPE41 protein complex induces significant (p<0.0001) B cell response in sera derived from TB patients and in mouse model as compared to the PE25 protein. Further, mice immunized with the PE25/PPE41 complex and PPE41 proteins showed significant (p<0.00001) proliferation of splenocyte as compared to the mice immunized with the PE25 protein and saline. Flow cytometric analysis showed 15-22% enhancement of CD8+ and CD4+ T cell populations when immunized with the PPE41 or PE25/PPE41 complex as compared to a marginal increase (8-10%) in the mice immunized with the PE25 protein. The PPE41 and PE25/PPE41 complex can also induce higher levels of IFN-gamma, TNF-alpha and IL-2 cytokines.


CONCLUSIONS
While this study documents the differential immunological response to the complex of PE and PPE vis-à-vis the individual proteins, it also highlights their potential as a candidate vaccine against tuberculosis.
Tundup
Smanla
S
Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Pathak
Niteen
N
Ramanadham
M
M
Mukhopadhyay
Sangita
S
Murthy
K J R
KJ
Ehtesham
Nasreen Z
NZ
Hasnain
Seyed E
SE
D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes / Q000276:immunology* / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D009876:Operon / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D046912:Multiprotein Complexes; C041832:proline transport protein; D018698:Glutamic Acid