Role of MHC class I pathways in Mycobacterium tuberculosis antigen presentation

Abstract

MHC class I antigen processing is an underappreciated area of nonviral host-pathogen interactions, bridging both immunology and cell biology, where the pathogen's natural life cycle involves little presence in the cytoplasm. The effective response to MHC-I foreign antigen presentation is not only cell death but also phenotypic changes in other cells and stimulation of the memory cells ready for the next antigen reoccurrence. This review looks at the MHC-I antigen processing pathway and potential alternative sources of the antigens, focusing on Mycobacterium tuberculosis (Mtb) as an intracellular pathogen that co-evolved with humans and developed an array of decoy strategies to survive in a hostile environment by manipulating host immunity to its own advantage. As that happens via the selective antigen presentation process, reinforcement of the effective antigen recognition on MHC-I molecules may stimulate subsets of effector cells that act earlier and more locally. Vaccines against tuberculosis (TB) could potentially eliminate this disease, yet their development has been slow, and success is limited in the context of this global disease's spread. This review's conclusions set out potential directions for MHC-I-focused approaches for the next generation of vaccines.

Keywords: MHC-I; Mycobacterium tuberculosis; antigen processing; cytotoxic T cells; host-pathogen interactions; vaccine.

Figure 1

Antigen processing for MHC-I presentation during the course of Mtb infection. The figure represents stages of phagocytosed bacilli (pathways are time- and site-specific). (I) The phagolysosome, which disables pathogen—presented antigens are from fragmented dead bacilli. (II) Persistent phagosomes where fusion with lysosome was blocked successfully by the bacilli—presented antigens are virulent factors released by live Mtb. (III) Autophagolysosomes with persistent latent bacilli—presented antigens are scanty and a by-product of pathogen–host cellular organelles interactions: (IIIa) stage of autophagosome nucleation initiation and (IIIb) a stage of persisting autophagolysosome via contact sites with ER and classical MHC-I antigen processing route. (IV) Cytosol bacilli—stage of active infection with Mtb overtaking cell innate defense, generalized disruption of cell functions, and likely progress to cell death. Dashed arrows represent pathogen transition; solid arrows represent sources of the antigen. Created with BioRender.com.