The PGRS Domain from PE_PGRS33 of Mycobacterium tuberculosis is Target of Humoral Immune Response in Mice and Humans

Area of Science:

• Immunology
• Microbiology
• Tuberculosis research

Background:

• The PE_PGRS33 protein is a key antigen in Mycobacterium tuberculosis, with immunomodulatory properties influenced by its PE and PGRS domains.
• The specific roles of the PE and PGRS domains in host immune recognition and their contribution to latent tuberculosis infection remain unclear.

Purpose of the Study:

• To investigate the immunogenic properties of the complete PE_PGRS33 protein and its individual PE and PGRS domains.
• To evaluate the immune response to PE_PGRS33 in both a mouse model and in humans with latent tuberculosis infection (LTBI).

Main Methods:

• Assessed antibody production, interferon-gamma (IFN-γ) secretion, and T-cell proliferation (CD4+ and CD8+) in BALB/c mice.
• Measured IFN-γ secretion and antibody responses in individuals with LTBI and non-infected vaccinated controls.

Main Results:

• In mice, both PE_PGRS33 and its domains induced comparable antibody and IFN-γ responses, but PE_PGRS33 and the PE domain showed higher T-cell proliferation.
• In humans, IFN-γ and antibody responses to PE_PGRS33 were observed in both LTBI and non-infected vaccinated individuals, with antibodies targeting the PGRS domain.
• T-cell responses to PE_PGRS33 domains differ, with the PE domain eliciting a stronger T-cell response in mice.

Conclusions:

• BCG vaccination induces T and B cell responses to PE_PGRS33 that persist in non-infected individuals, suggesting IFN-γ response may not solely indicate LTBI.
• The PE domain significantly contributes to T-cell activation, crucial for controlling tuberculosis, while the PGRS domain is targeted by antibodies.
• Findings clarify the distinct roles of PE and PGRS domains in the immune response to Mycobacterium tuberculosis.