ATP6V0E2, PRF1, GNLY and ME

The T-cell forms an immunological synapse with a target cell. Then vesicles containing perforin and cytotoxic enzymes are released to kill the target cell. Perforin forms small pores in the membrane of the target cell. The cytotoxic vesicles are acidic (pH 5,1 - 5,4), which prevents perforin activation. Activation of perforin requires a neutral pH environment (1).

Hypermethylated genes nr. 2 and nr. 3 associated with quality of life in ME patients are ATP6V0E2 and ATP6V0E2 antisense RNA1 (2).

The gene ATP6V0E2 encodes a component of vacuolar ATPase which mediates acidification of several intracellular compartments and secretory granules/vesicles. The v-ATPase is also called proton pump or H⁺- ATPase.

ATP6V0E2 is an isoform of the V0e subunit. Diverse physiological functions of the v-ATPase in different membranes are established through the utilization of specific subunit isoforms.

The genes PRF1 (perforin 1) and GNLY (granulysin) are hypermethylated and associated with quality of life in ME patients (2).

Granulysin is also present in the cytotoxic vesicles of T-cells. It has antimicrobial activity.

Is the hypermethylated ATP6V0E2 related to a "pH-situation" in the cytotoxic vesicles and/or in the immunological synapse?

References:

1. Kloc et al: The newly found functions of MTOC in immunological response. J Leucocyte Biology, 2014, 95.
2. Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11