HLA Class I molecules present intracellular (endogenous) antigens to CD8+ Cytotoxic T cells and/or Natural Killer Cells. Normal cellular processes involve intracellular proteases that ship intracellular peptides to the cell surface for immune system monitoring.
In normal CD8+ T cells, the Toll-like Receptor (TLR) interacts with the CD8 protein to restrict and selectively bind to HLA class I glycoproteins found on all nucleated cells to "screen" for foreign antigens. Virally-infected or cancer cells would produce non-self proteins. These non-self proteins are expressed in the binding domain of HLA class I with TLR/CD8 complex. This activates the CD8+ T cells to release cytolytic granules that trigger the bound cell to induce apoptosis (programmed cell death).
Some pathogens and diseases may dampen, or decrease, the expression of HLA class I proteins. This decreases the ability of CD8+ T cells to find virally-infected or cancer cells. Fortunately, these virally-infected or cancer cells do not escape from Natural Killer (NK) cells. Lack of HLA class I expression on viral or cancer host cells prevents the inhibition of CD56+ NK cells. Loss of HLA class I in a host cell provides no inhibitory signals to the NK cell, which activates NK cells to kill the targeted cell with a targeted release of apoptotic granules.
