Novel helper molecules and pathways of antigen presentation in tuberculosis
Research report (imported) 2003 - Max Planck Institute for Infection Biology
Tuberculosis is the most prevalent bacterial infectious disease and is caused by Mycobacterium tuberculosis. Protective immunity is mediated by T-lymphocytes including CD4 helper T cells, cytotoxic CD8 T cells as well as lipid-specific, CD1-restricted T-lymphocytes. Scientists from the Department of Immunology of the Max-Planck-Institute for Infection Biology now characterized a novel presentation pathway for mycobacterial antigens as prerequisite for effective CD8 T cell activation. This "detour pathway" originates from mycobacteria-infected macrophages undergoing programmed cell death (apoptosis). During apoptosis, infected macrophages release apoptotic vesicles containing mycobacterial material. Subsequently, these vesicles are taken up by dendritic cells, which process the engulfed antigens for presentation to CD8 T cells. Moreover, a new group of helper molecules named saposins was identified which facilitates antigen presentation of lipids through CD1-molecules. Saposins bridge the biophysical gap between membrane-bound lipids and hydrophilic presentation molecules. Lipid-specific T-lymphocytes play a role in tuberculosis since M. tuberculosis disposes of a waxy, lipid-rich cell wall. Insights into fundamental aspects of presentation of mycobacterial antigens are the basis for a better understanding of T cell activation and rational vaccine design against tuberculosis.