Guided example 1: ZAP70 as a potential target for immunosuppressive therapy

Background

ZAP70 is a cytoplasmic tyrosine kinase found mainly in T cells and is important both for T-cell development and for T-cell-receptor signalling (Figure 12). Its deficiency leads to severe combined immune disorder (SCID). ZAP70 is considered to be a relevant target for autoimmune disease, in which T-cell activation plays an important role. ZAP70 is also overexpressed in some individuals with chronic lymphocytic leukaemia, and these individuals have an especially poor prognosis. ZAP70 might therefore also be a useful therapeutic target in these patients.

Figure 12 T-cell-receptor signalling complex showing where ZAP70 fits into the signalling cascade. From the Reactome report on TCR signalling.

Scenario

Melissa is a discovery biologist at a major international pharmaceutical company working on autoimmune disease. She wants to be able to suppress activation of T cells following T-cell-receptor binding. She also wants to know what proteins are involved in T-cell signalling so that she can identify druggable targets. She has heard that ZAP70 is important for T-cell-receptor signalling and wants to find out more about it.