Exploring HLA-E restricted Mycobacterium tuberculosis specific T cells as vaccination targets for Tuberculosis

Abstract

Worldwide, a quarter of the population is infected with Mycobacterium tuberculosis (Mtb), the causative pathogen of the infectious disease Tuberculosis (TB). Each year, approximately 1 million people die from TB, making it the deadliest infectious disease in the world. There is currently only one vaccine available against TB, namely the Bacillus Calmette-Guérin (BCG) vaccine, which has been in use since 1921. However, BCG provides only limited protection against TB in adults. Therefore, a more effective vaccine is needed to stop the global pandemic. T cells can specifically recognize and eliminate Mtb-infected cells due to the interaction between the T cell receptor (TCR) and an HLA-molecule that presents a fragment of Mtb. However, there is significant genetic variation in classical HLA molecules among individuals, which complicates vaccination strategies aimed at inducing population wide T cell responses. In contrast, antigen presentation molecules exist with restricted genetic diversity, amongst them HLA-E. The aim of this thesis was to investigate the potential of HLA-E restricted T cells as vaccine targets for TB.