Immune regulation by Granzyme A and Granzyme escape mechanisms

Project leader: Prof Marieke van Ham PhD

Cytotoxic T cells and natural killer cells produce Granzyme A (GrzmA) and Granzyme B (GrzmB); effector molecules that cause apoptosis of target cells. Dendritic cells and many tumor cells are protected against GrzmB via expression of the GrzmB-inhibitor SerpinB9. Escape from GrzmA action is also likely to occur, but the mechanism is unknown. We have now identified the cellular mechanism that downmodulates the action of GrzmA in primary human cells and melanoma. In addition, we demonstrated that urinary GrzmA mRNA forms a biomarker for cellular rejection in kidney transplantation

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