Following occupancy of the T cell receptor by antigen, T cell proliferation and lymphokine production are determined by a second costimulatory signal delivered by a ligand expressed on antigen-presenting cells. SLAM (for signaling lymphocyte-activation molecule, also designated CDw150) is a novel receptor on T cells that, when engaged, potentiates T cell expansion in a CD28-independent manner. SAP (for SLAM-associated protein) contains an SH2 domain and functions to inhibit SH-PTP2 recruitment to the SLAM docking site, an activity induced by Fyn phosphorylation of SLAM. Mutations of the SAP gene may be associated with X-linked lympho-proliferative disease (XLP)