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.