MAJOR HISTOCOMPATIBILITY CLASS-I PRESENTATION OF SOLUBLE-ANTIGEN FACILITATED BY MYCOBACTERIUM-TUBERCULOSIS INFECTION

Cell-mediated immune responses are essential for protection against ma ny intraceIluIar pathogens. For Mycobacterium tuberculosis (MTB), prot ection requires the activity of T cells that recognize antigens presen ted in the context of both major histocompatibility complex (MHC) clas s II and I molecules. Since MHC class I presentation generally require s antigen to be localized to the cytoplasmic compartment of antigen-pr esenting cells, it remains unclear how pathogens that reside primarily within endocytic vesicles of infected macrophages, such as MTB, can e licit specific MHC class I-restricted T cells. A mechanism is describe d for virulent MTB that allows soluble antigens ordinarily unable to e nter the cytoplasm, such as ovalbumin, to be presented through the MHC class I pathway to T cells. The mechanism is selective for MHC class I presentation, since MTB infection inhibited MHC class II presentatio n of ovalbumin. The MHC class I presentation requires the tubercle bac illi to be viable, and it is dependent upon the transporter associated with antigen processing (TAP), which translocates antigenic peptides from the cytoplasm into the endoplasmic reticulum. The process is mimi cked by Listeria monocytogenes and soluble listeriolysin, a pore-formi ng hemolysin derived from it, suggesting that virulent MTB may have ev olved a comparable mechanism that allows molecules in a vacuolar compa rtment to enter the cytoplasmic presentation pathway for the generatio n of protective MHC class I-restricted T cells.