Signaling lymphocytic activation molecule (SLAM) is a family of genes. Homophilic binding between SLAMs is involved in cell-to-cell adhesion during antigen presentation. Signaling lymphocytic activation molecules are a CD2-related surface receptor expressed by activated phagocytes, T helper cells, and platelets. SLAMs have a variety of functions, including enhancing T cellular proliferation by stimulating IL-4 and IFN-gamma production. SLAM family (SLAMF) receptors can interact directly with microbes, which can cause phagocytic cells to migrate to the area. SLAMF activation can trigger

SLAM-associated protein SH2 domain–containing protein 1A is a protein that in humans is encoded by the ''SH2D1A'' gene. It is often called SLAM-associated protein (symbol SAP), where "SLAM" refers to signaling lymphocytic activation molecules. It is a SH2 domain–cont ...

(SAP) activation and a defective SAP can cause X-linked lymphoproliferative syndrome (XLP).

Family members

Members of the family include: *

SLAMF1 Signaling lymphocytic activation molecule 1 is a protein that in humans is encoded by the ''SLAMF1'' gene. Recently SLAMF1 has also been designated CD150 (cluster of differentiation 150). SLAMF1 belongs to the signaling lymphocytic activation mo ...

(CD150) *

SLAMF2 CD48 antigen (Cluster of Differentiation 48) also known as B-lymphocyte activation marker (BLAST-1) or signaling lymphocytic activation molecule 2 (SLAMF2) is a protein that in humans is encoded by the CD48 gene. CD48 is a member of the CD2 su ...

(CD48, FimH) * SLAMF3 (CD229, LY9) *

SLAMF4 CD244 (Cluster of Differentiation 244) is a human protein encoded by the gene. It is also known as Natural Killer Cell Receptor 2B4 This gene encodes a cell surface receptor expressed on natural killer cells (NK cells) (and some T cells) me ...

(CD244, 2B4) *

SLAMF5 CD84 (Cluster of Differentiation 84) is a human protein encoded by the gene. Function Members of the CD2 (see MIM 186990) subgroup of the Ig superfamily, such as CD84, have similar patterns of conserved disulfide bonds and function in adhes ...

(CD84) *

SLAMF6 SLAM family member 6 is a protein that in humans is encoded by the ''SLAMF6'' gene. The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is ...

(CD352) * SLAMF7 (CD319, CRACC) *

SLAMF8 SLAM family member 8 is a protein that in humans is encoded by the ''SLAMF8'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''b ...

(CD353) * SLAMF9

Location and function

SLAMFs are CD2-related surface receptors expressed by activated B and T cells, natural killer (NK) cells, dendritic cells, macrophages, eosinophils, neutrophils, and platelets, although different SLAMF receptors have varying expression patterns. SLAMF receptors are cell surface transmembrane molecules that can interact directly with microbes, which can cause phagocytic cells to migrate to the area.

and

are known to directly interact with outer membrane porins on gram negative bacteria.

is a known receptor for the measles virus and also serves as an

opsonin Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound. Thus, opsonins act as tags to label things in the body that should be phagocytosed (i.e. ...

for phagocytic cells, enhancing phagocytosis by localizing to phagosomes and inducing a signaling cascade resulting in enhanced fusion of phagosomes and lysosomes.

is known bind gram negative bacteria and is internalized after binding, promoting phagocytosis. SLAMFs are also involved in immune cell communication; SLAMFs are co-stimulatory molecules for both T-cells and NK cells. SLAMs enhance T helper cell proliferation by increasing IFN-gamma and IL-4 production.

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). The IgV and IgC2 domains are located on the extracellular portion of the receptor, while the ITSMs are used for signaling within the cell. SLAMFs can undergo alternative splicing, which can generate different isoforms of the SLAMF molecules that have different numbers of ITSMs and tyrosines, potentially with different functions. Proteins with SH2 domains are able to bind these ITSMs to initiate signaling cascades within the cell.

and

interact with one another, but all other SLAMF receptors are self-ligands, meaning that they interact with the corresponding receptor on other cells in a homophilic way.

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, through triggering

antibody-dependent cellular cytotoxicity Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose ...

(ADCC), and through NK cell activation via Ewing’s sarcoma-associated transcript 2 (EAT-2). EAT-2 is known to bind to phosphorylated tyrosines on ITSMs and alter cytokine production. Elotuzumab also blocks multiple myeloma cells from interacting with one another via the SLAMF7 ligand.

SLAM-associated protein (SAP)

The X-linked

(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 SLAM associated protein (SAP) causes X-linked lymphoproliferative syndrome (XLP), a frequently lethal 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.

References

{{Clear Genes on human chromosome 1 Single-pass transmembrane proteins