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Signaling lymphocytic activation molecules are a family of genes on the long arm of human chromosome 1. Homophilic binding between SLAMs is involved in cellular adhesion and SLAMs act as microbial sensors and are involved in cytokine production, B-cell activation, Natural Killer (NK) cell activity, macrophage response, and dendritic cell activity.

Family Members
Members of the family include:


 * SLAMF1 (CD150)
 * SLAMF2 (CD48, FimH, 2B4)
 * SLAMF3 (CD229, LY9)
 * SLAMF4 (CD244)
 * SLAMF5 (CD84)
 * SLAMF6 (CD352)
 * SLAMF7 (CD319, CRACC)
 * SLAMF8 (CD353)
 * SLAMF9

Location and Function
Signaling lymphocytic activation molecule (SLAM) is a CD2-related surface receptor expressed by activated T cells and B cells. SLAMs enhance T cellular proliferation and IFN-gamma production. SLAMF receptors are cell surface transmembrane molecules that can interact directly with microbes, which can cause phagocytic cells to migrate to the area. SLAMF1 and SLAMF6 are known to directly interact with outer membrane porins on gram negative bacteria. SLAMF1 also serves as an opsonin for phagocytic cells, enhancing phagocytosis by localizing to phagosomes and inducing a signaling cascade resulting in enhanced fusion of phagosomes and lysosomes. SLAMFs are also involved in immune cell communication; SLAMFs are co-stimulatory molecules for both T-cells and Natural Killer (NK) cells.

Structure
All members of the SLAMF family are classified as type I glycoproteins and share an amino-terminal IgV variable domain and a membrane-adjacent IgC2 constant domain, along with immunoreceptor tyrosine-based switch motifs (ITSMs). SLAMFs can undergo alternative splicing, which can generate different isoforms of the SLAMF molecules that have different numbers of ITSMs and tyrosines. SLAMF2 and SLAMF4 interact with one another, but all other SLAMF receptors are self-ligands.

Uses in Immunotherapy
SLAMFs are potential targets for immunotherapy. For example, elotuzumab is an anti-SLAMF7 humanized monoclonal antibody used to treat multiple myeloma. SLAMF7 is a self-ligand over-expressed in plasma cells of multiple myeloma patients. Elotuzumab stimulates NK cells to release granzyme through blocking SLAMF7, triggering antibody-dependent cellular cytotoxicity (ADCC) and through NK cell activation via Ewing’s sarcoma-associated transcript 2 (EAT-2). Elotuzumab also blocks multiple myeloma cells from interacting with one another via the SLAMF7 ligand.

SLAM-Associated Protein
The X-linked SLAM-associated protein (SAP), encoded by the SH2D1A gene, consists primarily of an SH2 domain which can interact with ITSMs present on most SLAMF receptors. Unlike most SH2 binding proteins, SAP does not require tyrosines on the ITSMs to be phosphorylated prior to binding. SAP is expressed in lymphocytes (specifically NK cells and T cells, but not usually B cells), eosinophils, and platelets. A defective SAP causes X-linked lymphoproliferative syndrome (XLP), a mononucleosis characterized by inability to respond to infection with Epstein-Barr virus (EBV), leading to a failure to clear B-cells infected with the virus, which can be fatal.