Sh2d1b1, also known as EAT-2, is a single SH2-domain adapter gene. It is involved in regulating the function of several immune cell types, particularly in the context of the 'signalling lymphocyte activation molecule' (SLAM) family-related signalling pathways. EAT-2 is expressed in innate immune cells like natural killer (NK) cells and has a significant role in the immune response [1,2].

Mice lacking or overexpressing EAT-2 were studied to understand its function in NK cells. EAT-2, like SAP, associated with the SLAM-related receptor 2B4 in NK cells. However, it was found to be an inhibitor of NK cell function, repressing natural cytotoxicity and interferon-γ secretion through tyrosine phosphorylation of its C terminus. In the absence of EAT-2, the SLAM family receptor CRACC, which is coupled to EAT-2, potently inhibited NK cell function. In contrast, when EAT-2 was present, CRACC positively regulated NK cell functions [2,4]. Also, mice lacking SAP, EAT-2 and ERT (members of the SAP family) showed that these adaptors together were essential for the elimination of hematopoietic cells by NK cells. Without SAP-related adaptors, SLAM receptors lost their activating function and became inhibitory, repressing other activating receptors like NKG2D [3].

In conclusion, Sh2d1b1 (EAT-2) plays a crucial role in fine-tuning NK cell responses and the surveillance of hematopoietic cells by NK cells. The study of gene-modified mouse models, such as those with EAT-2 knockout or overexpression, has provided valuable insights into its function in the immune system, especially in understanding the complex regulation of NK cell-mediated immune responses.