SLAMF1 - signaling lymphocytic activation molecule family member 1 | Elisa - Clia - Antibody - Protein

Background

SLAMF1, also known as CD150, is a membrane glycoprotein and member of the signaling lymphocytic activation molecule (SLAM) family, which plays a critical role in modulating immune responses. It is encoded by the SLAMF1 gene and is primarily expressed on the surface of several immune cells, such as T cells, B cells, macrophages, and dendritic cells. SLAMF1 functions as a self-ligand, allowing it to engage in homophilic interactions that are essential for intercellular communication in immune responses. It influences a variety of immune processes, including cell activation, proliferation, cytokine production, and cytotoxic functions. This molecule plays a significant role in adaptive immunity by regulating immune cell interactions, positioning it as a critical factor in the immune response to pathogens and in autoimmune conditions.

Protein Structure

SLAMF1 is a type I transmembrane protein comprising around 335 amino acids with an approximate molecular weight of 70-80 kDa. It is classified as an immunoglobulin (Ig) superfamily receptor, and its structure can be divided into three major domains:

Extracellular Domain (ECD):

• The extracellular domain of SLAMF1 consists of two immunoglobulin-like (Ig-like) domains: a distal variable-like (IgV) domain and a proximal constant-like (IgC) domain.
• The IgV domain is essential for homophilic interactions, allowing SLAMF1 molecules on adjacent immune cells to bind to each other, which facilitates immune synapse formation and signaling.
• This domain is also involved in binding with other SLAM-associated proteins (SAPs), which regulate downstream signaling pathways.
• SLAMF1 is heavily glycosylated, with multiple N-linked glycosylation sites that enhance its stability and facilitate proper folding, essential for its receptor-ligand interactions.

Transmembrane Domain (TMD):

• The transmembrane domain is composed of a single-pass α-helix that anchors the receptor to the cell membrane.
• This segment enables the structural integrity of SLAMF1 and interacts with other transmembrane proteins, which are important for mediating signal transduction processes and lateral organization within the cell membrane.

Cytoplasmic Domain:

• The cytoplasmic tail of SLAMF1 contains multiple tyrosine residues within immune receptor tyrosine-based switch motifs (ITSMs). These motifs are crucial for downstream signal transduction.
• The ITSMs allow SLAMF1 to interact with signaling molecules such as the SLAM-associated protein (SAP) and EWS/FLI1-activated transcript 2 (EAT-2), adapters that modulate intracellular signaling pathways involved in cell activation and cytokine production.
• These motifs are phosphorylated upon activation, recruiting SAP family members that facilitate signaling by linking SLAMF1 to various downstream effectors. SAP interaction is particularly critical for SLAMF1’s role in immune cell signaling and in modulating adaptive immune responses.

Classification and Subtypes

SLAMF1 belongs to the signaling lymphocytic activation molecule (SLAM) family within the immunoglobulin superfamily (IgSF). The SLAM family includes other receptors such as SLAMF2, SLAMF3, and SLAMF6, which share structural and functional similarities, particularly in immune cell interactions. The SLAM family members are primarily involved in immune modulation and cell-cell communication. SLAMF1 itself does not have distinct subtypes but interacts closely with other SLAM family members and signaling adapters that shape its immune functions.

Function and Biological Significance

Immune Cell Activation and Cytokine Production:

• SLAMF1 is involved in the activation and proliferation of various immune cells, including T cells, B cells, and natural killer (NK) cells. In T cells, SLAMF1 contributes to both Th1 and Th2 responses, while in B cells, it promotes antibody production and enhances the immune response.
• SLAMF1 ligation triggers cytokine production, including interferon-gamma (IFN-γ), particularly in NK and T cells. This cytokine production is critical in mounting a strong immune response against intracellular pathogens.

Cytotoxicity and Immune Regulation:

• SLAMF1 is essential in regulating the cytotoxic functions of NK cells and cytotoxic T cells. It enhances cytotoxicity by promoting the release of cytotoxic granules containing perforin and granzymes, thereby contributing to the destruction of infected or malignant cells.
• Through its interactions with SAP, SLAMF1 plays a role in immune synapse formation and stability, which are critical for effective cytotoxicity in NK cells.

Pathogen Recognition and Antimicrobial Defense:

• SLAMF1 facilitates the immune response to pathogens, particularly in the recognition of intracellular bacteria. It supports the engulfment of pathogens by macrophages, promoting their clearance.
• SLAMF1 can mediate phagolysosome formation in macrophages, an essential process in degrading engulfed pathogens. The receptor's involvement in phagocytosis helps clear pathogenic threats in innate immune responses.

Adaptive Immunity Modulation:

• SLAMF1 influences T and B cell interactions, which are essential for adaptive immunity. It modulates T-helper cell responses and can impact the balance of Th1/Th2 responses. In B cells, SLAMF1 supports antibody production and memory cell formation, which are crucial for long-term immunity.

Clinical Issues

Immunodeficiency Disorders:

• Mutations or deficiencies in SLAMF1 or SAP can lead to severe immunodeficiencies, such as X-linked lymphoproliferative syndrome (XLP). XLP is characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, leading to life-threatening immune dysregulation.
• In XLP patients, dysfunctional SLAMF1 signaling can impair cytotoxicity and immune regulation, causing uncontrolled lymphocyte proliferation and increased susceptibility to infections.

Autoimmune Diseases:

• Dysregulation of SLAMF1 signaling has been linked to autoimmune conditions like systemic lupus erythematosus (SLE). Overexpression of SLAMF1 can promote excessive cytokine production and immune cell activation, contributing to the pathological immune responses observed in autoimmune diseases.
• SLAMF1 may serve as a therapeutic target in autoimmune conditions, as modulating its activity could help restore immune balance and reduce inflammation.

Cancer and SLAMF1:

• SLAMF1 is implicated in certain cancers, particularly hematologic malignancies such as lymphomas and leukemias. Aberrant expression of SLAMF1 in these cancers may alter immune responses and support tumor cell survival.
• Therapeutic strategies targeting SLAMF1 are being explored to modulate immune responses in the tumor microenvironment, potentially enhancing anti-tumor immunity and improving responses to immunotherapy.

Infectious Diseases:

• SLAMF1 has a role in the immune response to several pathogens, including viruses and intracellular bacteria. Alterations in SLAMF1 expression or function can affect susceptibility to infections and may influence outcomes in conditions like HIV and tuberculosis.
• Research on SLAMF1 in infectious diseases focuses on understanding how manipulating SLAMF1 expression or signaling could enhance pathogen clearance and improve immunity.

Summary

SLAMF1, or CD150, is an Ig superfamily receptor primarily expressed on immune cells, where it modulates activation, proliferation, and immune synapse formation. Structurally, SLAMF1 contains extracellular Ig-like domains facilitating homophilic interactions, a single-pass transmembrane domain, and a cytoplasmic tail containing ITSM motifs crucial for intracellular signaling. Functionally, SLAMF1 regulates immune cell activation, cytotoxicity, and cytokine production, making it essential in both innate and adaptive immunity. It is involved in immune cell communication, phagocytosis, and pathogen clearance, and is implicated in autoimmune diseases, cancers, and immunodeficiencies. As a clinical target, SLAMF1 holds potential in immune-modulating therapies for treating autoimmune conditions, cancer, and infectious diseases.