T cells show immunity to a variety of bacteria

A study from Monash University, Australia found a group of divergent bacterial pathogensincluding pneumococci, all of which share a highly conserved small protein sequence, which is both displayed and recognized by human T cells in a population-wide conserved manner.

Typically, T cells of the immune system respond to a specific characteristic (antigen) of a microbe, thereby generating protective immunity. As reported in Immunityand the researchers found an exception to this rule.

The study aimed to understand the immune mechanisms that protect against pneumococcus, a bacterial pathobiont that can reside harmlessly in the upper respiratory mucous membranes but can also cause infectious diseases, which can range from middle ear and sinus infections to pneumococcal pneumonia and invasive bloodstream infections.

Most pneumococcal polysaccharide conjugate vaccines (PCVs) currently in use are effective against 10–13 serotypes, but increasing serotype replacement is becoming a problem. The World Health Organization (WHO) estimates that 1.6 million people die each year from pneumococcal disease, including 0.7 to 1 million children under the age of 5, most of whom live in countries in development.

The study co-led by the Monash Biomedicine Discovery Institute, 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 United, identified a crucial fragment of the pneumococcal toxin pneumolysin that was commonly presented by a particular class of human antigen-presenting molecules and recognized by the T cells of most people who naturally develop specific immunity to pneumococcal proteins.

The uniformly presented and widely recognized bacterial protein fragment was found not to be unique to pneumococcal pneumolysin, but was shared by a large family of so-called cholesterol-dependent (CDC) bacterial cytolysins. These are produced by divergent bacterial pathogens primarily affect humans and cause a range of respiratory, gastrointestinal or vaginal infectious diseases.

Pneumococci are in the background, an array of macrophages and dendritic cells are arranged around the central image of a T cell. Rows of TCRs interacting with the identified HLA-bound pneumolysin epitope (white) cross the length and width of the illustration, emphasizing their centrality in the immune response.
(Credit: Dr. Erica Tandori)

First author Dr Lisa Ciacchi said: “Using the national synchrotron was key to providing molecular insight into how T cell receptors see these conserved antigens when presented by common molecules of human leukocyte antigen (HLA)”.

Co-author Dr Martijn van de Garde explained: “We have yet to identify the exact function of the near-ubiquitous T-cell populations in relation to this conserved protein fragment commonly presented during colonizations or infections. underway by CDC-producing bacteria. Whether T cells have a cross-protective mode of action or have a tolerizing anti-inflammatory function remains to be investigated.”

Shared co-author Dr. Kristin Ladell said; “The identification of T cells that recognize a ubiquitous bacterial pattern using T cell receptors shared between individuals with prevalent HLAs is very exciting. The reagents generated for this study can now be used to study groups of patients to examine the prevalence of these shared TCRs and their link to immune protection.”

Continued investigations could inform the development of interventions for people to more effectively resist or eliminate CDC-linked bacterial diseases.