BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex–Specific Lipopeptides in Guinea Pigs

Abstract

A new class of highly antigenic, MHC-II–restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis–infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette-Guérin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies.

Mycobacterium tuberculosis lipoproteins in virulence and immunity – fighting with a double‐edged sword

“…Also, Kaufmann et al . hypothesize about a coevolution of M. tuberculosis with the immune system in which the recognition of lipopeptides leads to an immune response favouring the establishment of granulomas and with this a lifelong latent infection of the host and long‐term survival of the pathogen.…”

Recombinant Lipoprotein Rv1016c Derived from Mycobacterium tuberculosis Is a TLR-2 Ligand that Induces Macrophages Apoptosis and Inhibits MHC II Antigen Processing

“…However, MTB remains to survival within infected macrophages for prolonged periods by evading the elimination of host immune responses (Holvast et al, 2010; Dorhoi and Kaufmann, 2014). The molecular basis that allow MTB to persist for years in the face of vigorous CD4 + T cell responses may involve the decreased antigen processing or MHC-II expression in infected macrophages, which prevented the recognition of infected macrophages by effector CD4 + T cells (Noss et al, 2000; Kaufmann et al, 2016). Actually, MTB indeed can inhibit antigen processing by murine macrophages via a mechanism involving decreased synthesis of MHC-II molecules, consistent with other reports of the ability of mycobacteria to decrease MHC-II expression by infected cells (Kaufmann and Schaible, 2005; Pecora et al, 2009; Satchidanandam et al, 2014).…”

The current state of animal models and genomic approaches towards identifying and validating molecular determinants ofMycobacterium tuberculosisinfection and tuberculosis disease

“…Guinea pigs have also been useful in investigations of responses to antigenic lipopeptides due to their possession of type I CD1 presentation molecules (Kaufmann et al . 2016). Initially considered the gold standard for vaccine testing against TB, the guinea pig model is considered highly susceptible (Clark, Hall and Williams 2014) and has suffered from a lack of immunological tools such as guinea pig-specific antibodies for immune analysis in the past.…”