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Articles of Significant Interest Selected from This Issue by the Editors

T Cell Costimulation by CD6 Is Dependent on Bivalent Binding of a GADS/SLP-76 Complex T cell responses are regulated by CD6, a cell surface receptor. CD6-mediated functional effects include both activation and inhibition. Breuning and Brown (e00071-17) show that activating signals through the CD6 cytoplasmic region depend on direct cooperative binding of the intracellular adaptor proteins GADS and SLP-76 to two adjacent phosphorylated tyrosine motifs. Disabling this region of the cytoplasmic tail not only resulted in a loss of costimulation but also revealed inhibition by CD6, paving the way for further systematic dissection of the molecular interactions which will make it clear how CD6 contributes to both enhancement and restraint of immune responses.