Defining the molecular basis of CD4+ T cell receptor recognition of a Human Leukocyte Antigen (HLA)-DP restricted epitope from pneumolysin

Pneumolysin, a toxin released by the bacterial pathogen Streptococcus pneumoniae, which can cause life-threatening diseases including pneumonia, meningitis and sepsis. This toxin belongs to a family of cholesterol-dependent cytolysins (CDCs) produced by 28 different bacterial species. In this thesis, we reveal the molecular basis underlying immune cell recognition of an 11-amino acid long ‘undecapeptide’ sequence from pneumolysin, which is highly conserved across all CDCs. These findings provide a platform for possible immunotherapeutic approaches to prevent pneumococcal infections and potentially against infections with other CDC-producing pathogens.