The mouse Ly6 gene family encodes proteins found in lymphocytes and other cells. Some are involved in cell activation; no ligands have been found. A ligand for Ly6d (ThB) was identified on lymphocytes using microspheres loaded with Ly6d and the cDNA isolated from a spleen/thymus library by panning on Ly6d. The Ly6d ligand (Ly6d-L) is a nonglycosylated protein of 9 kDa of broad distribution, rich in cysteine, with no discernable transmembrane sequence. Its N and C termini are on the cell surface, where it associates with a 30 kDa protein. Ly6d-L is homologous with an EGF repeat of Notch.