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

Ingrid Cohen,Cristina Parada,Enrique Acosta-Gã­O,Clara Espitia

doi:10.3389/fimmu.2014.00236

Abstract

The PE_PGRS33 protein is a member of the PE family, which encompasses the PE and the PE_PGRS subfamilies. Among PE_PGRS’s, this protein is one of the most studied antigens and its immunomodulatory properties are influence by both PE and PGRS domains. However, the contribution of these domains to the host immune recognition of the PE_PGRS33 protein and their potential role in latent tuberculosis infection in humans is still unknown. In this study, the immunogenic properties of the complete PE_PGRS33 protein and each domain separately were evaluated in BALB/c mice and latent tuberculosis infected (LTBI) humans. In mice, PE_PGRS33 and its domains induced similar antibody production and secretion of IFN-γ. PE_PGRS33 and the PE domain stimulated higher CD4+ and CD8+ T-cell proliferation compared to the PGRS domain. This demonstrated that the principal difference in the immune recognition of the domains is the higher activation of T-cell subpopulations involved in the control of tuberculosis. In humans, the secretion of IFN-γ in response to PE_PGRS33 was detected in both LTBI and in non-infected vaccinated individuals. The same was observed for antibody response, which targets epitopes located in the PGRS domain but not in the PE domain. These observations suggest that T and B cell responses to PE_PGRS33 are induced by BCG vaccination and can be maintained for many years in non-infected individuals. This also indicates that the IFN-γ response detected might not be associated with latent tuberculosis infection. These results contribute to the elucidation of the role of the PE_PGRS33 protein and its PE and PGRS domains in the immune response against Mycobacterium tuberculosis.

Highlights

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is one of the most successful pathogens known
HUMORAL AND CELLULAR IMMUNE RESPONSE TO PE_PGRS33, THE PE, AND PGRS DOMAINS IN MICE Humoral immune response in mice Sera from immunized and control mice were tested using ELISA assay to determine the levels of antigen-specific Immunoglobulin G (IgG) antibodies against PE_PGRS33 and its PGRS and PE domains
The levels of IgG2a subclass against the PE domain were lower than the levels against the PGRS domain or the complete PE_PGRS33 protein (Figure 1C)

Summary

Introduction

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is one of the most successful pathogens known This bacterium is able to elude the host immune system and starts the disease after the infection or remains latent during long time [1]. Around 61 of these genes encodes for members of the PE_PGRS subfamily These proteins are characterized by a highly conserved PE domain of approximately 110 amino acid residues that contains the motif Pro–Glu (PE) near the N-terminus. This domain is followed by the PGRS (polymorphic GC-rich-sequence) domain, which varies in size from 100–1400 amino acid residues and is rich in repetitive Gly–Gly–X motifs [2]

Methods

Results

Conclusion