They make a supportive argument that Itk PH domain oligomerization and IP4 feedback are physiologically important, consistent with the severely defective TCR signaling, IP4 production, Itk/PLCγ1 activation, positive selection and resulting immunodeficiency in ItpkB−/− mice, the ability of IP4 to bimodally control Itk PH domain binding to PIP3in vitro, and the reported Itk PH domain oligomerization [2], [6], [7], [28]. This evidence concerns the gene ITK and immunodeficiency disease.