Researchers recently provided evidence against the belief that our immune system’s T cells respond to a specific microbial feature. In a study reported in Immunity, an international team of scientists found that a group of divergent bacterial pathogens, including pneumococci, share a small, highly conserved protein sequence presented and recognized by human T cells population wide. This discovery could help develop interventions for people to resist or clear cholesterol dependent cytolysins, or CDC, bacterial diseases more efficiently.
Pneumococcus is a bacterial pathobiont that can reside harmlessly in the upper respiratory mucosae but can also cause infectious diseases ranging from middle ear and sinus infections to pneumococcal pneumonia and invasive bloodstream infections, especially in infants and older adults. Although most currently used pneumococcal polysaccharide-based conjugate vaccines are effective against 10–13 serotypes, growing serotype replacement is becoming increasingly difficult.
The Monash Biomedicine Discovery Institute’s co-led study, in collaboration with the National Institute for Public Health and the Environment (RIVM) and Utrecht University in the Netherlands and Cardiff University in the UK, identified a crucial fragment of the pneumococcal toxin pneumolysin presented by a particular class of human antigen presenting molecules. Additionally, they found it was recognized by T cells in most individuals who naturally develop specific immunity to pneumococcal proteins.
The study found that the uniformly presented and broadly recognized bacterial protein fragment was not unique to pneumococcal pneumolysin but was shared by a large family of bacterial CDCs. These are produced by divergent bacterial pathogens mostly affecting humans and causing a range of respiratory, gastro-intestinal, or vaginal infectious diseases.
First author Dr. Lisa Ciacchi explains, “The use of the National synchrotron was key to provide molecular insight into how the T cell receptors see these conserved antigens when presented by common Human Leukocyte Antigen (HLA) molecules.”
Shared first author Dr. Martijn van de Garde adds, “We have not yet identified the exact function of the near-ubiquitous T cell populations to this commonly presented conserved protein fragment during ongoing colonizations or infections with CDC producing bacteria. Whether the T cells have a cross-protective mode of action or have an anti-inflammatory tolerizing function, remains to be investigated.”
Continuing investigations could unveil the prevalence of these shared TCRs and their relation to immune protection and could potentially help develop interventions for patients’ resistance against CDC-related bacterial diseases.
Overall, this study provides insight into immune mechanisms that protect against pneumococcus and other bacterial pathogens, which could ultimately help prevent diseases that cause morbidity and mortality worldwide.