SLAMF Immune Checkpoint Molecule for Drug Development
Introduction to SLAMF
Signaling lymphocytic activation molecules family (SLAMF), a group of nine cell surface receptors, is involved in regulating immune cell activation. These molecules are differentially expressed on a variety of immune cell types. Several are self-ligands, and SLAMF1 has been identified as the human measles virus receptor. The functional significance of SLAM family members is emphasized by their involvement in X-linked lymphoproliferative (XLP) disease.
Table.1 SLAM family of cell surface receptors.
CDw150, SLAM, signaling lymphocytic activation molecule family member 1
Thymocytes, platelets, mature DCs, naïve B cells, and memory T cells
Functions as a costimulatory molecule.
BCM1, BLAST, BLAST1, MEM-102, hmCD48 molecule
Lymphocytes, dendritic cells, and endothelial cells
Contribute to the formation of an immunological synapse between a T cell and an APC.
LY9, hly9, lymphocyte antigen 9
CD4+ CD8+, CD4-CD8-thymocytes, peripheral mature B cells and T cells
Interact with SH2D1A.
2B4, NAIL, NKR2B4, Nmrk, SLAMF4
NK cells, γδ T cells, monocytes, basophils, eosinophils
Activating receptor on NK cells.
LY9B, SLAMF5, hmCD84
NK cells, T cells, B cells, and eosinophils
Function in adhesion interactions between T lymphocytes and accessory cells.
KALI, KALIb, Ly108, NTB-A, NTBA, SF2000, SLAM family member 6
NK, T, and B lymphocytes
Function as a coreceptor in the process of NK cell activation.
19A, CRACC, CS1, SLAM family member 7
Normal plasma cells and malignant plasma cells
Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B.
BLAME, SBBI42, SLAM family member 8
May function during B cell lineage commitment.
CD2F10, CD84-H1, CD84 Homolog 1
May play a role in the immune response.
In general, SLAMF members are type I transmembrane glycoproteins containing a cytoplasmic tail, except CD48, a glycosylphosphatidylinositol (GPI) membrane anchor. SLAMF receptors are composed of an extracellular ectodomain formed by two Ig-like domains; one variable (V)-like domain lacking disulfide bonds followed by a truncated Ig constant 2 (C2)-like domain with two intradomain disulfide bonds, except SLAMF3, which possesses four Ig-like domains (two tandem repeats of V-Ig/C2-Ig sets).
Fig.1 Structural representation of the human SLAM family members. (Sintes, 2011)
SLAMF Members and Immune Responses
SLAMF receptors have been shown to modulate lymphocyte activation processes that are key elements in the initiation and progression of autoimmune diseases, such as the development of NKT cells, cytokine production in the thymus and periphery, NK- and CD8+ T- cell cytotoxicity, or germinal center-dependent antibody production. Lessons from genetic studies in mice have been key to support the hypothesis that SLAMF receptors function as disease modifiers and/or susceptibility factors of systemic autoimmunity. At present, several members have been regarded as drug targets in multiple disease models.
SLAM molecules are of particular interest for the diagnosis and therapy of various cancers. Targeting these molecules is already under clinical investigation and can open new therapeutic options to improve the management of cancer patients. Currently, the most advanced therapeutic strategy is targeting SLAMF7 using humanized monoclonal antibodies. Enriched with extensive scientific expertise, Creative Biolabs provides comprehensive immune checkpoint molecule analysis services to support your research project. For more service information, please refer to Service or directly contact us.
Sintes, J.; et al. SLAM Family Receptors and Autoimmunity. Autoimmune Disorders: Pathogenetic Aspects. 2011, 53.
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