Impaired Epstein-Barr virus-specific CD8+ T cell function in X-linked lymphoproliferative disease is restricted to SLAM family positive B cell targets.

International audienceX-linked lymphoproliferative disease (XLP) is a condition associated with mutations in the signaling lymphocytic activation molecule (SLAM) associated protein (SAP/SH2D1A). SAP functions as an adaptor, binding to and recruiting signaling molecules to SLAM family receptors expressed on T and NK cells. XLP is associated with extreme sensitivity to primary Epstein-Barr virus (EBV) infection, often leading to a lethal infectious mononucleosis. To investigate EBV-specific immunity in XLP patients, we studied five individuals who had survived EBV infection and found CD8+ T cell responses numerically comparable to healthy donors. However further investigation of in vitro derived CD8+ T cell clones established from two of these donors showed they efficiently recognized SLAM-ligand-negative target cells expressing EBV antigens, but showed impaired recognition of EBV-transformed, SLAM-ligand-positive, lymphoblastoid cell lines (LCLs). Importantly, LCL recognition was restored when interactions between the SLAM receptors CD244 and NTBA and their ligands on LCLs were blocked. We propose that XLP patients' particular sensitivity to EBV, and not to other viruses, reflects at least in part EBV's strict tropism for B lymphocytes and the inability of the CD8+ T cell response often to contain the primary infection of SLAM ligand-expressing target cells