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.

Principle Name	CD Name	Alternative Names	Expression	Major Function
SLAMF1	CD150	CDw150, SLAM, signaling lymphocytic activation molecule family member 1	Thymocytes, platelets, mature DCs, naïve B cells, and memory T cells	Homotypic binding. Functions as a costimulatory molecule.
SLAMF2	CD48	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.
SLAMF3	CD229	LY9, hly9, lymphocyte antigen 9	CD4⁺ CD8⁺, CD4-CD8-thymocytes, peripheral mature B cells and T cells	Interact with SH2D1A.
SLAMF4	CD244	2B4, NAIL, NKR2B4, Nmrk, SLAMF4	NK cells, γδ T cells, monocytes, basophils, eosinophils	Activating receptor on NK cells.
SLAMF5	CD84	LY9B, SLAMF5, hmCD84	NK cells, T cells, B cells, and eosinophils	Function in adhesion interactions between T lymphocytes and accessory cells.
SLAMF6	CD352	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.
SLAMF7	CD319	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.
SLAMF8	CD353	BLAME, SBBI42, SLAM family member 8	lymphoid tissues	May function during B cell lineage commitment.
SLAMF9	/	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.

Reference

Sintes, J.; et al. SLAM Family Receptors and Autoimmunity. Autoimmune Disorders: Pathogenetic Aspects. 2011, 53.

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